WO2025248488A1 - Compositions and methods for preventing and treating healthcare-associated candida auris infections with dual antigen vaccine - Google Patents

Abstract

Presented herein, in certain embodiments, are compositions and methods for preventing and/or treating multi-drug-resistant fungal infections such as Candida auris infectious via using a dual antigen vaccine composition of A1s3p and Hyr1p antigens. The vaccine compositions are useful in preventing and/or treating a fungal infection, such as Candida albicans, Candida auris, or Gram-negative bacterial infections, and/or a fungal-bacterial mixed infection. These infections can be mucosal or invasive infections.

Description

Attorney Docket No.022098-0583845 COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING HEALTHCARE-ASSOCIATED CANDIDA AURIS INFECTIONS WITH DUAL ANTIGEN VACCINE FIELD OF THE INVENTION [0001] The embodiments relate to antibody compositions and methods for preventing or treating multi-drug resistance (MDR) infectious diseases in a subject, particularly for treating a fungal infection, such as Candida albicans, Candida auris, or Gram-negative bacterial infections, and/or a fungal-bacterial mixed infections. More particularly, the embodiments relate to immune therapeutic methods using a combination of Als3p and Hyr1p antigens to formulate a vaccine useful in preventing and/or treating a fungal infection, such as Candida albicans, Candida auris, or, Gram-negative bacterial infections, and/or a fungal-bacterial mixed infection. GOVERNMENT SUPPORT [0002] This work was supported in part by National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) grant number 1R01AI141202, and the NIAID Preclinical Service. The Federal Government may have certain rights in the invention. BACKGROUND OF THE INVENTION [0003] Multi-drug resistance is often associated with bacterial infections and rarely with fungal infections. Healthcare-associated infections (HAIs) are increasingly drug-resistant, lethal, and costly. The emergence and re-emergence of MDR pathogens characterize current global trends in Healthcare-associated infections (HAIs). Boucher HW, et al., “Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America,” Clinical Infectious Diseases, 48(1):1–12 (2009); Spellberg B, et al., “The Epidemic of Antibiotic- Resistant Infections: A Call to Action for the Medical Community from the Infectious Diseases Society of America,” Clinical Infectious Diseases, 46(2):155–164 (2008); Higgins PG, et al., “Global spread of carbapenem-resistant Acinetobacter baumannii,” J. Antimicrob. Chem, 65(2):233–238 (2009); Rosenthal VD, et al., “International Nosocomial Infection Control Consortium (INICC) report, data summary for 2003-2008,” Am J Infect Control, 38(2):95-104.e2 (2010); Collin B, et al., “Antifungal resistance in non- albicans Candida species,” Drug Resistance Updates 1999;2(1):9–14 (1999); Edmond MB, et al., “Nosocomial Attorney Docket No.022098-0583845 Bloodstream Infections in United States Hospitals: A Three‐Year Analysis,” Clinical Infectious Diseases, 29(2):239–244 (1999); Millar BC, et al., “Community-associated MRSA (CA-MRSA): an emerging pathogen in infective endocardit–--authors’ response,” J. Antimicrob. Chem, 61(4):967–968 (2008); and Valencia R, et al., “Nosocomial Outbreak of Infection With Pan–Drug-Resistant Acinetobacter baumanniiin a Tertiary Care University Hospital,” Infection Control & Hospital Epidemiology, 30(3):257–263 (2009). There are ~1.0 million HAIs in the US, associated with 70,00-100,000 deaths and $30B in healthcare costs. Klevens RM, et al., “Estimating health care-associated infections and deaths in U.S. Hospitals, 2002. Public Health Reports [Internet],” Public Health Rep, 122(2):160–166 (2007); Magill SS, et al., “Multistate Point-Prevalence Survey of Health Care–Associated Infections. New England Journal of Medicine [Internet],” N Engl J Med, 370(13):1198–1208 (2014). [0004] Candida is the most common cause of invasive fungal infections in the United States and other countries with advanced medical technology. Rangel‐Frausto MS, et al., “National Epidemiology of Mycoses Survey (NEMIS)...,” Clinical Infectious Diseases, 29(2):253–258 (1999). Candida spp. (including those caused by the predominant C. albicans) are now statistically tied with Enterococcus as the third most frequent nosocomial bloodstream isolates, (Wisplinghoff H, et al., “Current trends in the epidemiology of nosocomial bloodstream infections...,” Clin Infect Dis., 36(9):1103–10 (2003); Wisplinghoff H, et al., “Nosocomial bloodstream infections in US hospital...,” Clin Infect Dis., 39(3):309–17 (2004); and Wisplinghoff H, et al., “Nosocomial bloodstream infections in pediatric patients in United States hospitals...,” Pediatr Infect Dis J., 22(8):686–691 (2003), surpassing the incidence of bacteremia caused by Escherichia coli or Klebsiella species. Even with antifungal therapy, disseminated candidiasis has a ~40% mortality rate. Ala-Houhala M, et al., “Clinical and microbiological factors associated with mortality in candidemia in adult patients 2007-2016,”. Infect Dis., 51(11–12):824–830 (2019); Lortholary O, et al., “Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010),” Intensive Care Med., 40(9):1303–12 (2014). The cost associated with hematogenously disseminated candidiasis is estimated to be $2-4 billion/year in the United States. Miller LG, et al., “Estimating the Cost of Nosocomial Candidemia in the United States,” Clinical Infectious Diseases, 32(7):1110–1110 (2001); Wilson LS, et al., “The Direct Cost and Incidence of Systemic Fungal Infections,” Value in Health, 5(1):26–34 (2002); and Attorney Docket No.022098-0583845 Zaoutis TE, et al., “The Epidemiology and Attributable Outcomes of Candidemia in Adults and Children ...,” Clinical Infectious Diseases, 41(9):1232–1239 (2005). [0005] Candida auris has emerged as a significant threat to global health, having been reported in >140 countries across six continents. C. auris is known to harbor resistance mechanisms to multiple classes of antifungal drugs (e.g., azole, echinocandin, and polyene classes) which makes it challenging to treat, leading to increased morbidity, mortality (with ~60% reported mortality rates), (Lockhart SR, et al., “Simultaneous emergence of multidrug- resistant candida auris ...,” Clin Infect Dis., 64(2):134–140 (2017)), and healthcare costs. Chowdhary A, et al., “The lurking scourge of multidrug resistant Candida auris in times of COVID-19 pandemic,” J Glob Antimicrob Resist, 22:175–176 (2020). C. auris can easily spread and colonize inanimate objects and human skin in healthcare settings and poses a risk to immunosuppressed patients staying in such contaminated healthcare facilities (for example intensive care units [ICU] or nursing homes) causing healthcare-associated infections (HAIs). Further, diagnosis of Candida spp. is particularly challenging and often leads to a delay in diagnosis, making treatment even more difficult. C. auris evolved simultaneously mainly in four major geographical regions: South Asia (Clade I), East Asia (Clade II), Africa (Clade III), and South America (Clade IV). [0006] C. auris can infect the immunosuppressed patient population through attached invasive medical devices and surgical procedures. Once C. auris gains access to the bloodstream, it can disseminate to the kidney, heart, and other target organs. C. auris bloodstream infection is very difficult to treat and has a very high mortality rate of up to ~60%. More recently, the widespread use of corticosteroid therapy to manage COVID-19- related infections resulted in the rise of COVID-19-associated fungal infections including C. auris. Consequently, the U.S. Centers for Disease Control and Prevention (CDC) declared C. auris as an “urgent threat to public health” in its recent antimicrobial drug resistance report (AMR). [0007] C. auris has shown a wide range of drug resistance mechanisms (mutations in ERG genes involved in ergosterol synthesis, efflux pump upregulations, etc.) across all clades, thus making it difficult to develop new drug variants within the existing antifungal class (azoles, polyenes, and echinocandins). It has been established that 90% and 30% of the clinical isolates are resistant to at least one or two antifungal drugs, respectively, while several Attorney Docket No.022098-0583845 clinical isolates are resistant to all clinically available antifungal drugs and are therefore untreatable. [0008] Gram-negative bacteria are responsible for half of all HAIs in the US. In particular, Acinetobacter baumannii (AB) has emerged as a predominant cause of MDR HAIs ^{22–30, 36-45} Of great concern, 40-70% of AB isolates are now extensively drug-resistant (XDR) (resistant to all antibiotics except colistin and tigecycline)^{1,4,22,23,31,32}. Infections caused by XDR AB are associated with >60% mortality for bloodstream infections^32–35. Some strains are resistant to all FDA-approved antibiotics and are hence untreatable. Similarly, infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) are a major clinical concern due to their increasing number in HAIs and to the increasing resistance to nearly all currently available antibiotics including the last line antibiotic, colistin.^36–38. CPKP represents ~40% of all K. pneumonia HAIs^39–41. These infections are associated with high mortality rates ⁴². [0009] HAIs display well-characterized and shared risk factors and facilitate multivalent vaccine strategies. Risk factors for HAIs are known, and these infections often occur in the same patient populations. Patients who are at risk of developing AB, CPKP, and/or Candida infections include those who are: 1) colonized with the pathogen; 2) catheterized; 2) in the ICU; 3) diabetic; 4) neutropenic; 5) taking steroids; 5) suffering from burns, surgical wounds, and trauma; 6) on mechanical ventilation; and 7) receiving broad-spectrum antimicrobial drugs^{26–30,33,43–69}. Many patients have an intact immune system with effector cells required for active vaccine solutions^70–73. Critically, many HAIs occur as late-onset disease, allowing for vaccine-mediated protective immunity to develop. For example, patients treated with antibiotics and on mechanical ventilators develop AB after 30 days of stay^54,74–76. Similarly, the mean time to onset disseminated candidiasis is 22 days of hospitalization⁷⁶. [0010] The past few decades provide evidence that the development of resistance to antibiotics is inevitable. Thus, there is a need to develop novel anti-infective approaches that do not rely solely on a drug’s antibacterial action. In this context, boosting the patient’s immunity through vaccines and immunomodulators is a promising new adjunctive and/or alternative therapeutic concept. Vaccines are the only practical strategy to eliminate certain diseases, exemplified by smallpox and polio. [0011] Vaccines and other therapies effective in preventing and/or treating pathogenic infections have been described previously. For example, Ibrahim, et al., U.S. Patent No. Attorney Docket No.022098-0583845 10,160,790 discloses methods and compositions for vaccinating against candidiasis and Acinetobacter infections or both that include an isolated polypeptide of hyphal regulated protein (Hyr1p) or an immunogenic fragment thereof, in a pharmaceutically acceptable medium. The disclosure of U.S. Patent No.10,160,790 is incorporated by reference herein in its entirety. Similarly, Yu, et al., U.S. Patent No.8,709,446 discloses the use of Hyphal regulated cell wall protein 1 (Hyr1) as a vaccine target for combatting disseminated candidiasis. The disclosure of U.S. Patent No.8,709,446 is incorporated by reference herein in its entirety. In addition, Ibrahim, et al., U.S. Patent No.10,130,691 discloses compositions and methods for treating fungal and bacterial pathogens in which the compositions comprise fragments of Als3 or Hyr1. The disclosure of U.S. Patent No.10,130,691 is incorporated by reference herein in its entirety. There still exists a need to develop vaccines suitable to prevent invasive candidiasis, and candidemia, due to Candida spp., including those caused by C. auris and C. albicans, as well as infections and disorders caused by other bacterial pathogens. [0012] The embodiments disclosed herein address these and other needs readily apparent to those skilled in the art. The emergence of multi-drug resistance in fungal pathogens such as C. auris and others including bacteria pathogens highlights the importance of developing alternative measures to combat infections and disorders caused by these pathogens. Therefore, alternative therapeutic approaches are urgently needed. SUMMARY [0013] In accordance with an embodiment, there are provided compositions, vaccines, and methods of ameliorating and/or preventing a fungal infection or a fungal-bacterial mixed infection in a mammal comprising administering to the mammal a composition or vaccine comprising therapeutically effective amounts of C. albicans recombinant Als3p and Hyr1p, or one or more fragments thereof, in a pharmaceutically acceptable medium. [0014] The embodiments also provide a vaccine for preventing and/or treating a fungal infection or fungal-bacterial mixed infection that comprises therapeutically effective amounts of C. albicans recombinant Als3p and Hyr1p, or one or more fragments thereof, in a pharmaceutically acceptable medium. Additional embodiments include methods of treating and/or preventing fungal infections by administering a composition comprising therapeutically effective amounts of C. albicans recombinant Als3p and Hyr1p, or one or Attorney Docket No.022098-0583845 more fragments thereof, in a pharmaceutically acceptable medium, in combination with, or as an adjunctive therapy to antifungal drugs. Another embodiment includes a combination of an antifungal drug and a composition comprising therapeutically effective amounts of C. albicans recombinant Als3p and Hyr1p, or one or more fragments thereof, in a pharmaceutically acceptable medium. BRIEF DESCRIPTION OF THE DRAWINGS [0015] The drawings illustrate embodiments of the technology and are not limiting. For clarity and ease of illustration, the drawings are not made to scale and, in some instances, various aspects may be shown exaggerated or enlarged to facilitate an understanding of particular embodiments. [0016] FIG.1 shows the efficacy of a recombinant Als3-based Alhydrogel®-adjuvanted (NDV-3A) vaccine in protecting women <40 years of age with history of recurrent vulvovaginal candidiasis (RVVC) due to C. albicans from relapse for up to 12 months when vaccinated with a single dose. | [0017] FIG.2 shows the structural homology of C. albicans Als3p and Hyr1p, as well as their shared cross-protective epitopes in C. auris and Gram (-) bacteria. Active vaccine based on Als3p and Hyr1p protects mice against C. auris and AB infection, respectively. Passive immunization by monoclonal antibody targeting a shared epitope protects mice against both C. auris and KP. [0018] FIG.3 shows Anti-Als3 and anti-Hyr1 IgG titers in Alum, CAF01 liposomal adjuvant-antigen, or BDX formulations. CD-1 mice (N= 5/group) vaccinated SC or Intranasal (BDX100 formulations) with different vaccine formulations (Als3 and Hyr1 antigens ratio on x-axis) on day 0 and 21. Two weeks after final vaccination, serum IgG titers were evaluated using ELISA. [0019] FIG.4 shows the frequency of Als3 or Hyr1-specific T cells. Mean frequency (n=5 mice/cell/formulation) of Als3 or Hyr1-specific Th1, Th2 and Th17 cells (IFN-gamma, IL-4 or IL17 producing cells) in mice vaccinated with Alum, CAF01, or BDX100 vaccine Attorney Docket No.022098-0583845 formulations are shown in the heat-map. Each row represent data from each vaccine formulation. [0020] FIG.5 illustrates the animal study designs for evaluating the efficacy of a vaccine described in the embodiments in preventing and/or treating infections caused by C. albicans, C. auris, and Gram (-) bacteria. [0021] FIG.6 illustrates the survival efficacy of a vaccine described in the embodiments (CAF01 + Als3/Hyr1) against hematogenously disseminated infections due to C. auris and C. albicans. Mice were vaccinated on Days 1 and 21 and IV challenged 14 days post-boost. Mice (>10 Mice/group) survivals were compared after 21 days post-infection by Mantel-Cox test. [0022] FIG.7 provides a graphical representation of how the vaccine described in the embodiments (CAF01 + Als3/Hyr1) with antigen ratios of 30/10 and 10/10 prevented weight loss due to systemic candidiasis and AB pneumonia. CD-1 mice (N=9-10/group) weights were compared after 4 days of infection by Mann-Whitney Test (Median + IQR). [0023] FIG.8 illustrates the reduction of tissue microbial burden in mice infected with C. auris by administering a vaccine described in the embodiments (CAF01 + Als3/Hyr1) 10µg/10µg. Two weeks after vaccination, CD-1 mice (N=9-10/group) were infected with C. auris. Tissue microbial burdens were determined 4 days post-infection and compared by Mann-Whitney test (Median ±IQR). [0024] FIG.9 shows the mechanism of vaccine mediated protection using a vaccine described in the embodiments (CAF01 + Als3/Hyr1) 10µg/10µg. Naïve mice or vaccinated mice were infected with A. C. albicans, B. C. auris or C. A. baumannii. Naïve mice (n= 10 mice /group) received two injections of vaccine or placebo sera on days 0 and +7 relative to infection. Vaccinated or placebo mice (n= 10 mice /group) received anti-CD4 or isotype control antibodies to deplete the CD T cells. For C. albicans mice were vaccinated three times (Days 0, 21, 35) and for other infections only two times (days 0 and 21). For C. auris and A. baumannii infections the mice were immunosuppressed with cyclophosphamide and cortisone acetate. The mice were infected with target pathogens after 14 days of final vaccination. Mice survivals were compared after 21 days post-infection by Mantel-Cox test. Attorney Docket No.022098-0583845 [0025] FIG.10 shows the durable immune response after one or two booster immunizations with a vaccine described in the embodiments (CAF01 + Als3/Hyr1) 10µg/10µg. Vaccine antigen-specific immunity (IgG endpoint titer and T cells producing IFN-g or IL-4 or IL-17) was monitored at different time points relative to final booster immunization, using ELISA and FluroSpot assays. Data presented as mean ±SE of N=5 mice/group. [0026] FIG.11 provides a flow chart of Upstream (left) and Downstream Processes (right) for Als3 manufacturing. [0027] FIG.12 provides a comparison between a dual vaccine described in the embodiments (CAF01 + Als3/Hyr1) and vaccines of each antigen alone (30 µg antigen dose) in vaccination against C. albicans hematogenously disseminated infections. [0028] FIG.13 provides a comparison between a dual vaccine described in the embodiments (CAF01 + Als3/Hyr1) and vaccines of each antigen alone (10 µg antigen dose) in vaccination against C. albicans hematogenously disseminated infections. [0029] Figure 14A shows the efficacy of different adjuvant vaccine formulations against C. albicans, and Figure 14B shows the efficacy of different adjuvant vaccine formulations against C. auris. DETAILED DESCRIPTION [0030] The present embodiments feature compositions and uses thereof in preventing and/or treating fungal and bacterial and fungal-bacterial infections. In an embodiment the composition comprises at least a Candida HYR1 polypeptide antigen, or an immunogenic fragment thereof, an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, and an acceptable adjuvant. HYR1 is a hyphae co-expressed gene, the null mutant strain of which does not display any morphologic abnormality in vitro. Als3p polypeptide can be a Candida albicans Als3p (for example, as described in U.S. Patent No.10,653,757, or an immunogenic fragment thereof). In other embodiments, the Als3p polypeptide includes the N-terminal domain of Candida albicans Als3p or an immunogenic fragment thereof. [0031] In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “includes,” Attorney Docket No.022098-0583845 “including,” and the like. “Consisting essentially of or “consists essentially” likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments. Subjects [0032] The term “subject” refers to animals, typically mammalian animals. Any suitable mammal can be treated by a method or composition described herein. Non-limiting examples of mammals include humans, non-human primates (e.g., apes, gibbons, chimpanzees, orangutans, monkeys, macaques, and the like), domestic animals (e.g., dogs and cats), farm animals (e.g., horses, cows, goats, sheep, pigs) and experimental animals (e.g., mouse, rat, rabbit, guinea pig). In some embodiments, a mammal is a human. A mammal can be any age or at any stage of development (e.g., an adult, teen, child, infant, or a mammal in utero). A mammal can be male or female. A mammal can be a pregnant female. In certain embodiments a mammal can be an animal disease model, for example, animal models used for the study of fungal infection, and/or bacterial infection. [0033] “Patient” or “subject in need thereof” refers to a living organism suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, a patient is human. [0034] In some embodiments, a subject in need of a treatment or composition described herein is a subject at risk of intestinal disease and/or a subject that has an intestinal disease. In some embodiments, a subject in need of a treatment or composition described herein is a subject at risk of inflammatory bowel disease and/or a subject that has an inflammatory disease. In some embodiments, a subject in need of a treatment or composition described herein is infected with, or is suspected of being infected with a Candida pathogen, or a bacterial pathogen. In certain embodiments a composition described herein is used to treat or Attorney Docket No.022098-0583845 prevent a Candida infection or Candida propagation in a subject or a subject at risk of acquiring an intestinal disease. [0035] In some embodiments a subject or mammal is “at risk” of acquiring a fungal infection or a fungal-bacterial mixed infection. A mammal that is at risk may have increased risk factors for acquiring a bacterial infection, non-limiting examples of which include immunocompromised individuals or immune deficient subjects (e.g., bone marrow transplant recipients, irradiated individuals, subjects having certain types of cancers, particularly those of the bone marrow and blood cells (e.g., leukemia, lymphoma, multiple myeloma), subjects with certain types of chronic infections (e.g., HIV, e.g., AIDS), subjects treated with immunosuppressive agents, subjects suffering from malnutrition and aging, subjects taking certain medications (e.g. disease-modifying anti-rheumatic drugs, immunosuppressive drugs, glucocorticoids), subjects undergoing chemotherapy, the like or combinations thereof). In some embodiments a subject at risk is, will be, or has been in a location or environment suspected of containing fungus such as Candida auris, or, both Candida auris and Gram- negative bacteria. For example, a subject at risk can be a medical professional that is providing care to another who is suspected of being infected with, or known to be infected with fungus such as Candida auris. In certain embodiments, a subject at risk is any subject that has been exposed to fungus such as Candida auris. In certain embodiments, a subject at risk is any patient who is, will be, or has been in a hospital or medical care facility suspected of containing fungus such as Candida auris. In some embodiments a subject in need of a treatment or composition described herein is a subject at risk of a fungal infection or a fungal- bacterial mixed infection and/or a subject that has a fungal infection or a fungal-bacterial mixed infection. In some embodiments a subject in need of a treatment or composition described herein is infected with, or is suspected of being infected with a fungal infection or a fungal-bacterial mixed infection. In certain embodiments an antibody or the like or composition described herein is used to treat or prevent a fungal infection or a fungal- bacterial mixed infection in a subject or a subject at risk of acquiring a fungal infection or a fungal-bacterial mixed infection. Attorney Docket No.022098-0583845 Candida species [0036] In some embodiments, the Candida strain is Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Candida parapsilosis, or Candida auris. In some embodiments, the Candida strain is Candida albicans. In some embodiments, the Candida strain is Candida krusei. In some embodiments, the Candida strain is Candida tropicalis. In some embodiments, the Candida strain is Candida glabrata. In some embodiments, the Candida strain is Candida parapsilosis. In some embodiments, the Candida strain is Candida auris. [0037] The terms “Candida” as used herein refers to a genus of yeasts and is the most common cause of fungal infections worldwide Many species are harmless commensals or endosymbionts of hosts including humans; however, when mucosal barriers are disrupted or the immune system is compromised, they can invade and cause disease, known as an opportunistic infection. Candida is located on most mucosal surfaces and mainly the gastrointestinal tract, along with the skin. Candida albicans is the most commonly isolated species and can cause infections (candidiasis or thrush) in humans and other animals. [0038] The term “candidiasis” as used herein refers to a fungal infection due to any type of Candida. Signs and symptoms of candidiasis vary depending on the area affected. Most candida infections result in minimal complications such as redness, itching, and discomfort, though complications may be severe or even fatal if left untreated in certain populations. In healthy (immunocompetent) persons, candidiasis is usually a localized infection of the skin, fingernails or toenails (onychomycosis), or mucosal membranes, including the oral cavity and pharynx (thrush), esophagus, and the genitalia (vagina, penis, etc.); less commonly in healthy individuals, the gastrointestinal tract, urinary tract, and respiratory tract are sites of Candida infection. Common symptoms of gastrointestinal candidiasis in healthy individuals are anal itching, belching, bloating, indigestion, nausea, diarrhea, gas, intestinal cramps, vomiting, and gastric ulcers. Perianal candidiasis can cause anal itching; the lesion can be red, papular, or ulcerative in appearance, and it is not considered to be a sexually transmissible disease. Abnormal proliferation of the candida in the gut may lead to dysbiosis. This alteration may be the source of symptoms generally described as the irritable bowel syndrome, and other gastrointestinal diseases. Gram negative bacteria Attorney Docket No.022098-0583845 [0039] In some embodiments Gram negative bacteria refers to any pathogenic or potentially pathogenic strain or isolate of Gram-negative bacteria capable of causing an infection in a subject. For diagnostic embodiments, Gram negative bacteria may refer to any pathogenic, potentially pathogenic or non-pathogenic strain or isolate of Gram-negative bacteria. In some embodiments Gram negative bacteria refer to any strain or isolate of Gram-negative bacteria that displays resistance to one or more drugs (e.g., anti-bacteria drugs) or anti-bacteria treatments. In certain embodiments Gram negative bacteria is a strain or isolate that is resistant to multiple drugs (e.g., a multi-drug resistant strain). Non-limiting examples of gram negative bacteria include bacteria of the Acinetobacter genus, such as A. baumannii, A. iwoffii, A. haemolyticus, A. calcoaceticus, A. johnsonii, A. radioresistens, and A. junii, bacteria of the Haemophilus genus, such as H. aegyptius, H. aphrophilus, H. avium, H. ducreyi, H. felis, H. haemolyticus, H. influenza, H. parainfluenzae, H. paracuniculus, H. parahaemolyticus, H. pittmaniae, and H. somnus, bacteria of the Bordetella genus, such as B. ansorpii, B avium, B. bronchiseptica, B. hinzii, B. holmesii, B. parapertussis, B. pertussis, B. petrii, and B. trematum, bacteria of the Salmonella genus, such as S. typhimurium, S. bongori, S. enterica subsp. enterica, S. enterica subsp. salamae, S. arizonae, S. enterica subsp. diarizonae, S. enterica subsp. houtenae, and S. enterica subsp. indica, bacteria of the Yersina genus, such as Yersina pseudotuber, Y aldovae, Y aleksiciae, Y bercovieri, Y enterocolitica, Y frederiksenii, Y intertnedia, Y kristensenii, Y tnollaretii, Y pestis, Y pseudotuberculosis, Y rohdei, and Y ruckeri, bacteria of the Escherichia genus, such as E. albertii, E. blattae, E. coli, E. fergusonii, E. hermannii and E. vulneris, bacteria of the Pedobacter genus, such as P heparinus, P. roseus sp. nov. and P aquatilis sp. nov, bacteria of the Pseudomonas genus, such as P aeruginosa, P alcaligenes, P mendocina, P fluorescens, P monteilii, P oryzihabitans, P luteola, P putida, P cepacia, P. stutzeri, P maltophilia, P putrefaciens, P. mallei and P. pseudomallei, or bacteria of the Klebsiella genus, such as K pneumoniae, K. planticola K. oxytoca and K rhinoscleromatis. In some embodiments, a Gram- negative bacteria is K. pneumoniae, and any drug resistant or multi-drug resistant strain or isolate of Gram-negative bacteria (e.g., any strain or isolate of Gram negative bacteria that is resistant to one or more anti-bacterial medications). For example, in some embodiments, provided herein are methods of treating or preventing infections caused by K. pneumoniae. In some embodiments Gram-negative bacteria are carbapenem-resistant Gram-negative bacteria. In some embodiments Gram-negative bacteria are strains or isolates of Gram-negative bacteria Attorney Docket No.022098-0583845 that do not display resistance to a drug (e.g., an anti-bacteria medication) or anti-bacteria treatment. [0040] Any suitable Gram-negative bacterial infection can be prevented or treated by a method or composition herein. Gram negative bacterial infections can be systemic and/or local. Non-limiting examples of local Gram-negative bacterial infections include infections of the skin (epidermis, dermis, hypodermis, subcutaneous tissue), epithelial membranes, sinus membranes, ears, eyes, nose, throat, mouth, scalp, feet, nails, vagina, endometrium, urinary tract (e.g., bladder, urethra), the like, portions thereof or combinations thereof. Non-limiting examples systemic Gram-negative bacterial infections include infection of one or more tissues or organs, non-limiting examples of which include liver, kidney, heart, muscle, lung, stomach, large intestine, small intestine, testis, ovaries, brain, nervous tissue, blood, lymph, lymph nodes, salivary glands, the like or combinations thereof. [0041] A “effective amount” is an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signaling pathway, or reduce one or more symptoms of a disease or condition). An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). A “prophylactically effective amount” of a drug is an amount of a drug that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or their symptoms. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. An “activity decreasing amount,” as used herein, refers to an amount of antagonist required to decrease the activity of an enzyme relative to the absence of the antagonist. A “function disrupting amount,” as used herein, refers to the amount of antagonist required to disrupt the function of an enzyme or protein relative to the absence of the antagonist. The exact amounts will depend on the purpose of the Attorney Docket No.022098-0583845 treatment, and will be ascertainable by one skilled in the art using known techniques, along with the guidelines provided herein (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). [0042] As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan. Candida adhesin polypeptides [0043] In some embodiments, the therapeutical antibody specifically binds to HYR1, or an HYR1 polypeptide, or a fragment thereof. [0044] The term “HYR1” or “Hyr1” or “Hyr1p” as provided herein refers to the Hyphally regulated cell wall protein 1, a GPI-anchored hyphal cell wall protein expressed on hyphae and required for virulence. HYR1 is involved in innate immune cell evasion through confering resistance to neutrophil killing. HYR1 binds kininogen, the proteinaceous kinin precursor, and contributes to trigger the kinin-forming cascade on the cell surface. Production of kinins is often involved in the human host defense against microbial infections. Exemplary amino acid sequences for HYR1 include GENBANK® Accession Nos. KAF6069517.1, KAF6069516.1, and Q5AL03.2, which are all incorporated herein by reference. The full- length sequence for native C. albicans SC5314 Hyr1, GenBank AOW26950.1 is provided below as SEQ ID NO: 1:

Attorney Docket No.022098-0583845 [0045] The term “HYR1” or “Hyr1” or “Hyr1p” as used herein includes any of the recombinant or naturally-occurring forms of Hyphally regulated cell wall protein 1, or variants or homologs thereof that maintain HYR1 activity (e.g., within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to HYR1). In some aspects, the variants or homologs have at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring HYR1 protein. Attorney Docket No.022098-0583845 [0046] The term “Hyr1p” also includes an “Hyr1p fragment,” which is meant to denote a portion of the Hyr1 polypeptide containing fewer than 937, 936, or 935 amino acids. Preferred HYR1 fragments are between 300 and 350 or 250 to 500 amino acids in length. Desirably, the fragment is fewer than 937, 936, 935, 934, 933, 932, 931, or 930, 920, 910, 900, 890, 880, 870, 860, 850, 840, 830, 820, 810, 800, 790, 780, 770, 760, 750, 740, 730, 720, 710, 700, 690, 680, 670, 660, 650, 640, 630, 620, 610, 600, 590, 580, 570, 560, 550, 540, 530, 520, 510, 500, 490, 480, 470, 460, 450, 440, 430, 420, 410, 400, 390, 380, 370, 360, 350, 340, 330, 320, 310, 300, 290, 280, 270, 260, 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, or 10 amino acids, and desirably, is immunogenic. A HYR1 fragment, for example, may contain one or more conservative amino acid substitutions in the sequence of SEQ ID NO: 3. Additional desirable HYR1 fragments contain one or more conservative amino acid substitutions in the sequence of SEQ ID NO: 3 and/or at least one flanking amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 flanking amino acids) at the N- and/or C-terminus of the sequence of SEQ ID NO: 3. Other preferred HYR1 fragments contain seven or more continuous amino acids of the sequence of SEQ ID NO: 3. [0047] Non-limiting examples of a HYR1 fragment include amino acids 1-40, 10-50, 20-60, 30-70, 40-80, 50-90, 60-100, 70-110, 80-120, 90-130, 100-140, 110-150, 120-160, 130-170, 140-180, 150-190, 160-200, 170-210, 180-220, 190-230, 200-240, 210-250, 220-260, 230- 270, 240-280, 250-290, and 260-300, 270-310, 280-320, and 290-331 amino acids of the sequence of SEQ ID NO: 1 and these fragments having one or more of the following features: one or more conservative amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 conservative amino acid substitutions) in the sequence of SEQ ID NO: 1; one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 amino acids) truncated from the N and/or C-terminus of the sequence of SEQ ID NO: 1; and at least one flanking amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 flanking amino acids) at the N- and/or C-terminus of the sequence of SEQ ID NO: 1. [0048] In some embodiments, the Hyr1 or Hyr1 polypeptide comprises an amino acid sequence of SEQ NO: 2 (LKNAVTYDGPVPNN). In other embodiments the Hyr1 or Hyr1 polypeptide is one or more of the Hyr1 or Hyr1 polypeptides disclosed in U.S. Patent No. 8,709,446, the disclosure of which is incorporated by reference herein in its entirety, including the sequence listing therein. One specific Hyr1 polypeptide useful in the Attorney Docket No.022098-0583845 embodiments is the following polypeptide antigen disclosed in 8,709,446, which includes amino acids 25-350 of the Hyr1p of SEQ ID NO: 1): SEQ ID NO: 3: 1 TSRIDRGGIQ GFHGDVKVHS GATWAILGTT LCSFFGGLEV EKGASLFIKS DNGPVLALNV 61 ALSTLVRPVI NNGVISLNSK SSTSFSNFDI GGSSFTNNGE IYLASSGLVK STAYLYAREW 121 TNNGLIVAYQ NQKAAGNIAF GTAYQTITNN GQICLRHQDF VPATKIKGTG CVTADEDTWI 181 KLGNTILSVE PTHNFYLKDS KSSLIVHAVS SNQTFTVHGF GNGNKLGLTL PLTGNRDHFR 241 FEYYPDTGIL QLRAAALPQY FKIGKGYDSK LFRIVNSRGL KNAVTYDGPV PNNEIPAVCL 301 IPCTNGPSAP ESESDLNTPT TSSIET [0049] Other Hyr1 polypeptides useful in the embodiments include fragments of SEQ ID NO: 3, and polypeptides having one or more conservative amino acid substitutions in the sequence of SEQ ID NO: 3. Another specific Hyr1 polypeptide useful in the embodiments is the following polypeptide disclosed in 10,130,691, which includes amino acids 154-350 of the Hyr1p of SEQ ID NO: 1: SEQ ID NO: 4: 1 QNQKAAGNIA FGTAYQTITN NGQICLRHQD FVPATKIKGT GCVTADEDTW IKLGNTILSV 61 EPTHNFYLKD SKSSLIVHAV SSNQTFTVHG FGNGNKLGLT LPLTGNRDHF RFEYYPDTGI 121 LQLRAAALPQ YFKIGKGYDS KLFRIVNSRG LKNAVTYDGP VPNNEIPAVC LIPCTNGPSA 181 PESESDLNTP TTSSIET [0050] The term “Als3” as provided herein refers to the Agglutinin-like sequence protein 3, a cell surface adhesion protein (or invasin protein) which mediates Candida hyphal adherence and invasion to host tissues. Als3 plays an important role in the biofilm formation and pathogenesis of C. albicans infections. Als3 is necessary for C. albicans to bind to N- cadherin on endothelial cells and E-cadherin on oral epithelial cells and subsequent endocytosis by these cells. During disseminated infection, Als3 mediates initial trafficking to the brain and renal cortex and contributes to fungal persistence in the kidneys. Vaccination against the Als3 adhesin (NDV-3A vaccine) protected mice from the exacerbatory effect of C. albicans in a mouse DSS model of colitis. NDV-3A vaccinated mice also displayed decreased C. albians adherence of colon tissue during colonization of mice. ALS3 gene expression was also suppressed by intestinal adaptive immune responses in mouse models. Als3 is also targeted by intestinal IgA responses in both mouse models and in human fecal samples. Exemplary amino acid sequences for Als3 include GENBANK® Accession Nos. Attorney Docket No.022098-0583845 AOW31402.1 , XP_710435.2, and AAO72959.1, which are all incorporated herein by reference. The full-length sequence for native C. albicans SC5314 Als3p, GenBank AOW31402.1 is provided below as SEQ ID NO: 5 [0051] The term “Als3” as used herein includes any of the recombinant or naturally- occurring forms of Agglutinin-like sequence protein 3, or variants or homologs thereof that maintain Als3 activity (e.g., within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Als3). In some aspects, the variants or homologs have at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across Attorney Docket No.022098-0583845 the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Als3 protein. [0052] The term “Als3p” denotes an agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, including those disclosed in U.S. Patent No.10,653,757, the disclosure of which is incorporated by reference in its entirety, including the sequence listing therein. By “Als3p fragment” or “fragment of a Als3p” is meant a portion of a Als3p polypeptide containing fewer than 1050, 1025, 1000, 975, 950, or 945 amino acids. In some embodiments, Als3p fragments are between 300 and 350 or 250 to 500 amino acids in length. In some embodiments, the fragment is fewer than 1050, 1025, 1000, 975, 950, or 945, 940, 937, 936, 935, 934, 933, 932, 931, or 930, 920, 910, 900, 890, 880, 870, 860, 850, 840, 830, 820, 810, 800, 790, 780, 770, 760, 750, 740, 730, 720, 710, 700, 690, 680, 670, 660, 650, 640, 630, 620, 610, 600, 590, 580, 570, 560, 550, 540, 530, 520, 510, 500, 490, 480, 470, 460, 450, 440, 430, 420, 410, 400, 390, 380, 370, 360, 350, 340, 330, 320, 310, 300, 290, 280, 270, 260, 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, or 10 amino acids, and, in some instances, is immunogenic. [0053] In an embodiment, the Als3p antigen is an Als3p fragment derived from the N- terminal domain of Candida albicans agglutinin-like sequence 3 protein (Als3p), wherein the N-terminal domain extends from the end of the signal peptide to the beginning of the tandem repeats of the Candida albicans Als3p. One particular Als3p antigen includes an antigen represented by SEQ ID NO: 6 below: SEQ ID NO: 6: 1 KTITGVFNSF NSLTWSNAAT YNYKGPGTPT WNAVLGWSLD GTSASPGDTF TLNMPCVFKF 61 TTSQTSVDLT AHGVKYATCQ FQAGEEFMTF STLTCTVSNT LTPSIKALGT VTLPLAFNVG 121 GTGSSVDLED SKCFTAGTNT VTFNDGGKKI SINVDFERSN VDPKGYLTDS RVIPSLNKVS 181 TLFVAPQCAN GYTSGTMGFA NTYGDVQIDC SNIHVGITKG LNDWNYPVSS ESFSYTKTCS 241 SNGIFITYKN VPAGYRPFVD AYISATDVNS YTLSYANEYT CAGGYWQRAP FTLRWTGYRN 301 SDAGSNGIVI VATTRTVTDS TTAVTTLPFD PNRDKTKTIE ILKPIPTTTI TTSYVGVTTS 361 YLTKTAPIGE TATVIVDIPY HTTTTVTSKW TGTITSTTTH TNPTDSIDTV IVQVPL Attorney Docket No.022098-0583845 [0054] In addition, Als3p fragments, for example, may contain one or more conservative amino acid substitutions in a sequence, e.g., SEQ ID NO: 5 or SEQ ID NO: 6. Additional desirable Als3p fragments contain one or more conservative amino acid substitutions in a sequence shown in SEQ ID NO: 5 or SEQ ID NO: 6, and/or at least one flanking amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 flanking amino acids) at the N- and/or C-terminus of a sequence shown in SEQ ID NO: 5 or SEQ ID NO: 6. Other preferred Als3p fragments contain seven or more continuous amino acids of a sequence shown in SEQ ID NO: 5 or SEQ ID NO: 6. [0055] Non-limiting examples of an Als3p fragment include amino acids 1-40, 10-50, 20- 60, 30-70, 40-80, 50-90, 60-100, 70-110, 80-120, 90-130, 100-140, 110-150, 120-160, 130- 170, 140-180, 150-190, 160-200, 170-210, 180-220, 190-230, 200-240, 210-250, 220-260, 230-270, 240-280, 250-290, and 260-300, 270-310, 280-320, and 290-331 amino acids of a sequence shown SEQ ID NO: 5; and these fragments having one or more of the following features: one or more conservative amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 conservative amino acid substitutions); one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 amino acids) truncated from the N and/or C-terminus of a sequence of SEQ ID NO: 5; and at least one flanking amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 flanking amino acids) at the N- and/or C-terminus of a sequence shown in SEQ ID NO: 5 or SEQ ID NO: 6. [0056] The term “isolated” used as a modifier of a composition means that the composition is made by the hand of man or is separated from one or more other components in a naturally occurring in vivo environment, typically by one or more manipulative steps or processes. Generally, compositions so separated are substantially free of one or more materials with which they normally associate with in nature, for example, one or more protein, nucleic acid, lipid, carbohydrate, cell membrane. Thus, an isolated composition is separated from other biological components in the cell of the organism in which the composition naturally occurs, or from the artificial medium in which it is produced (e.g., synthetically or through cell culture). For example, an isolated anti-Hyr1p antibody can be obtained from an animal in which the antibody is produced (e.g., a non-transgenic mammal or a transgenic mammal, such as a rodent (mouse) or an ungulate (bovine) animal) and is separated from other polypeptides and nucleic acid. Thus, serum containing the antibody obtained from the animal is considered isolated. The term “isolated” does not exclude alternative physical forms, for Attorney Docket No.022098-0583845 example, an isolated antibody could include antibody subsequences, chimeras, multimers, or derivatized forms. [0057] The terms “invasin” and “invasin protein” as used herein refers to a protein belonging to a class of proteins associated with the penetration of pathogens into host cells. Invasins play a role in promoting entry during the initial stage of infection. [0058] The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ- carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. The terms “non-naturally occurring amino acid” and “unnatural amino acid” refer to amino acid analogs, synthetic amino acids, and amino acid mimetics which are not found in nature. [0059] Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes. [0060] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues, wherein the polymer may be conjugated to a moiety that does not consist of amino acids. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. A "fusion protein" refers to a chimeric protein encoding two or more separate protein sequences that are recombinantly expressed as a single moiety. Attorney Docket No.022098-0583845 [0061] As may be used herein, the terms “nucleic acid,” “nucleic acid molecule,” “nucleic acid oligomer,” “oligonucleotide,” “nucleic acid sequence,” “nucleic acid fragment” and “polynucleotide” are used interchangeably and are intended to include, but are not limited to, a polymeric form of nucleotides covalently linked together that may have various lengths, either deoxyribonucleotides or ribonucleotides, or analogs, derivatives or modifications thereof. Different polynucleotides may have different three-dimensional structures, and may perform various functions, known or unknown. Non-limiting examples of polynucleotides include a gene, a gene fragment, an exon, an intron, intergenic DNA (including, without limitation, heterochromatic DNA), messenger RNA (mRNA), transfer RNA, ribosomal RNA, a ribozyme, cDNA, a recombinant polynucleotide, a branched polynucleotide, a plasmid, a vector, isolated DNA of a sequence, isolated RNA of a sequence, a nucleic acid probe, and a primer. Polynucleotides useful in the methods of the disclosure may comprise natural nucleic acid sequences and variants thereof, artificial nucleic acid sequences, or a combination of such sequences. [0062] A polynucleotide is typically composed of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); and thymine (T) (uracil (U) for thymine (T) when the polynucleotide is RNA). Thus, the term “polynucleotide sequence” is the alphabetical representation of a polynucleotide molecule; alternatively, the term may be applied to the polynucleotide molecule itself. This alphabetical representation can be input into databases in a computer having a central processing unit and used for bioinformatics applications such as functional genomics and homology searching. Polynucleotides may optionally include one or more non-standard nucleotide(s), nucleotide analog(s) and/or modified nucleotides. [0063] Use of the terms "isolated" and/or "purified" in the present specification and claims as a modifier of DNA, RNA, polypeptides or proteins means that the DNA, RNA, polypeptides or proteins so designated have been produced in such form by the hand of man, and thus are separated from their native in vivo cellular environment. [0064] "Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, "conservatively modified variants" refers to those nucleic acids that encode identical or essentially identical amino acid sequences. Because of the degeneracy of the genetic code, a number of nucleic acid sequences will encode any given protein. For instance, the codons GCA, GCC, GCG and Attorney Docket No.022098-0583845 GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence. [0065] As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the disclosure. [0066] The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)). [0067] By “substantially identical” is meant a polypeptide exhibiting at least 50%, desirably 60%, 70%, 75%, or 80%, more desirably 85%, 90%, or 95%, and most desirably 99% amino acid sequence identity to a reference amino acid sequence. The length of comparison sequences will generally be at least 10 amino acids, desirably at least 15 contiguous amino acids, more desirably at least 20, 25, 50, 75, 90, 100, 150, 200, 250, 275, 300, 310, 315, 320, 325, 330, 335, 340, 345, or 350 contiguous amino acids, and most desirably the full-length amino acid sequence. Attorney Docket No.022098-0583845 [0068] Sequence identity may be measured using sequence analysis software on the default setting (e.g., Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705). Such software may match similar sequences by assigning degrees of homology to various substitutions, deletions, and other modifications. Multiple sequences may also be aligned using the Clustal W(1.4) program (produced by Julie D. Thompson and Toby Gibson of the European Molecular Biology Laboratory, Germany and Desmond Higgins of European Bioinformatics Institute, Cambridge, UK) by setting the pairwise alignment mode to “slow,” the pairwise alignment parameters to include an open gap penalty of 10.0 and an extend gap penalty of 0.1, as well as setting the similarity matrix to “blosum.” In addition, the multiple alignment parameters may include an open gap penalty of 10.0, an extend gap penalty of 0.1, as well as setting the similarity matrix to “blosum,” the delay divergent to 40%, and the gap distance to 8. Fungal infections, fungal-bacterial mixed infection and treatment or prevention of the same [0069] In some embodiments, the subject is suffering from, suspected of suffering from, or at risk of developing a fungal infection or a fungal-bacterial mixed infection. In some embodiments, the fungal infection or the fungal-bacterial mixed infection is caused by Candida auris. In some embodiments, the fungal-bacterial mixed infection is caused in part by Gram negative bacteria. [0070] The term “fungal condition” or “fungal infection” as used herein refers to fungal diseases, infection, or colonization including superficial mycoses (i.e., fungal diseases of skin, hair, nail and mucous membranes; for example, ringworm or yeast infection), subcutaneous mycoses (i.e., fungal diseases of subcutaneous tissues, fascia and bone; for example, mycetoma, chromomycosis, or sporotichosis), and systemic mycoses (i.e., deep- seated fungal infections generally resulting from the inhalation of air-borne spores produced by causal molds; for example, zygomycosis, aspergillosis, cryptococcosis, candidiasis, histoplasmosis, coccidiomycosis, paracoccidiomycosis, fusariosis (hyalohyphomycoses), blastomycosis, penicilliosis or sporotrichosis. [0071] The term “fungal-bacterial mixed infection” as used herein refers to mixed infections in a subject, such infections include any fungal infection as described above and any bacterial infection, particularly a Gram negative bacterial infection as described herein. Attorney Docket No.022098-0583845 It was known that fungal-bacterial interactions frequently occur during infections. For example, Pseudomonas aeruginosa is more frequently detected in individuals suffering from persistent Aspergillus fumigatus infection or persistent Candida albicans colonization than in patients without these fungi in their bronchoalveolar lavage. Furthermore, Candida infection is often tested with bacterial infection at the same time. Other studies reported that up to 38% of candidemia cases were mixed infections. [0072] The term “Candida” refers to any Candida species that can cause infection or disease when introduced into a subject. In some embodiments, the Candida species is Candida auris or Candida albicans. It is known that there are a large number of Candida species. Key Candida species which may be targeted by the antibodies described herein include Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis (a clonal complex of three species - C. parapsilosis, C. orthopsilosis and C. metapsilosis), and Candida krusei (synonym: Issatchenkia orientalis). Less-prominent species include Candida guilliermondii, Candida lusitaniae, Candida kefyr, Candida famata (synonym: Debaryomyces hansenii), Candida inconspicua, Candida rugosa, Candida dubliniensis, Candida norvegensis, Candida auris, and Candida haemulonii. [0073] The term “treating” or “treatment,” as it is used herein is intended to mean an amelioration of a clinical symptom indicative of a fungal infection or a fungal-bacterial mixed infection. Amelioration of a clinical symptom includes, for example, a decrease or reduction, or an inhibition, in at least one symptom of a fungal infection or a fungal-bacterial mixed infection in a treated individual compared to pretreatment levels or compared to an individual with a fungal condition, and/or an intestinal disease such inflammatory bowel syndrome, Crohn’s disease, or ulcerative colitis. The term “treating” also is intended to include the reduction in severity of a pathological condition, a chronic complication or an opportunistic fungal infection which is associated with a fungal infection or a fungal-bacterial mixed infection. Such pathological conditions, chronic complications or opportunistic infections are exemplified below. It will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration may be required. For example, the compositions are administered to the Attorney Docket No.022098-0583845 subject in an amount and for a duration sufficient to treat the patient. In embodiments, the treating or treatment is no prophylactic treatment. [0074] The term “preventing” or “prevention,” as it is used herein is intended to mean a forestalling of a clinical symptom indicative of a fungal infection or a fungal-bacterial mixed infection. Such forestalling includes, for example, the maintenance of normal physiological indicators in an individual at risk of infection by a fungus or fungi prior to the development of overt symptoms of the condition or prior to diagnosis of the condition. Therefore, the term “preventing” includes the prophylactic treatment of individuals to guard them from the occurrence of a fungal infection or a fungal-bacterial mixed infection. Preventing a fungal infection or a fungal-bacterial mixed infection in an individual also is intended to include inhibiting or arresting the development of the fungal condition. Inhibiting or arresting the development of the condition includes, for example, inhibiting or arresting the occurrence of abnormal physiological indicators or clinical symptoms such as those described above and/or well known in the art. Therefore, effective prevention of a fungal infection or a fungal- bacterial mixed infection would include maintenance of normal body temperature, weight, psychological state as well as lack of lesions or other pathological manifestations in an individual predisposed to a fungal infection or a fungal-bacterial mixed infection. Individuals predisposed to a fungal infection or a fungal-bacterial mixed infection include an individual who is immunocompromised, for example, but not limited to, an individual with AIDS, azotemia, diabetes mellitus, diabetic ketoacidosis, neutropenia, bronchiectasis, emphysema, TB, lymphoma, leukemia, or burns, or an individual undergoing chemotherapy, bone marrow-, stem cell- and/or solid organ transplantation or an individual with a history of susceptibility to a fungal condition. Inhibiting or arresting the development of the condition also includes, for example, inhibiting or arresting the progression of one or more pathological conditions, chronic complications or susceptibility to an opportunistic infection associated with a fungal condition. Pharmaceutical Compositions [0075] In some embodiments a pharmaceutical composition comprises at least a Candida HYR1 polypeptide antigen, or an immunogenic fragment thereof, an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, and an acceptable adjuvant. In one embodiment, the pharmaceutical composition comprises at least Hyr1p of SEQ ID NO: 1, Als3p of SEQ ID NO: 5, and an acceptable adjuvant. In another Attorney Docket No.022098-0583845 embodiment, the pharmaceutical compositions comprises at least an Hyr1p fragment of SEQ ID NO.: 4, an Als3p fragment of SEQ ID NO: 6, and an acceptable adjuvant. In certain embodiments, acceptable pharmaceutical compositions are nontoxic to recipients at the dosages and concentrations employed. A pharmaceutical composition can be formulated for a suitable route of administration. In some embodiments a pharmaceutical composition is formulated for subcutaneous (s.c.), intradermal, intramuscular, intraperitoneal and/or intravenous (i.v.) administration. In certain embodiments, a pharmaceutical composition can contain formulation materials for modifying, maintaining, or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In certain embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates (e.g., phosphate buffered saline) or suitable organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta- cyclodextrin); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counter ions (such as sodium); solvents (such as glycerin, propylene glycol or polyethylene glycol); diluents; excipients and/or pharmaceutical adjuvants (Remington's Pharmaceutical Sciences, 18th Ed., A.R. Gennaro, ed., Mack Publishing Company (1995)). [0076] In certain embodiments, a pharmaceutical composition comprises a suitable excipient, non-limiting example of which include anti-adherents (e.g., magnesium stearate), binders, fillers, monosaccharides, disaccharides, other carbohydrates (e.g., glucose, mannose or dextrins), sugar alcohols (e.g., mannitol or sorbitol), coatings (e.g., cellulose, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose, synthetic polymers, shellac, gelatin, corn protein zein, enterics or other polysaccharides), starch (e.g., potato, maize or wheat starch), silica, colors, disintegrants, flavors, lubricants, preservatives, sorbents, sweetners, vehicles, suspending agents, surfactants and/or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapal), stability enhancing agents (such as sucrose or sorbitol), and tonicity enhancing agents (such as alkali metal halides,sodium or potassium Attorney Docket No.022098-0583845 chloride, mannitol, sorbitol), and/or any excipient disclosed in Remington's Pharmaceutical Sciences, 18th Ed., A.R. Gennaro, ed., Mack Publishing Company (1995). [0077] In some embodiments a pharmaceutical composition comprises a suitable pharmaceutically acceptable additive and/or carrier. Non-limiting examples of suitable additives include a suitable pH adjuster, a soothing agent, a buffer, a sulfur-containing reducing agent, an antioxidant and the like. Non-limiting examples of a sulfur-containing reducing agents include those having a sulfhydryl group such as N-acetylcysteine, N- acetylhomocysteine, thioctic acid, thiodiglycol, thioethanolamine, thioglycerol, thiosorbitol, thioglycolic acid and a salt thereof, sodium thiosulfate, glutathione, and a C1-C7 thioalkanoic acid. Non-limiting examples of an antioxidant include erythorbic acid, dibutylhydroxytoluene, butylhydroxyanisole, alpha -tocopherol, tocopherol acetate, L- ascorbic acid and a salt thereof, L-ascorbyl palmitate, L-ascorbyl stearate, sodium bisulfite, sodium sulfite, triamyl gallate and propyl gallate, as well as chelating agents such as disodium ethylenediaminetetraacetate (EDTA), sodium pyrophosphate and sodium metaphosphate. Furthermore, diluents, additives and excipients may comprise other commonly used ingredients, for example, inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium phosphate, potassium phosphate and sodium bicarbonate, as well as organic salts such as sodium citrate, potassium citrate and sodium acetate. [0078] The pharmaceutical compositions used herein can be stable over an extended period of time, for example on the order of months or years. In some embodiments a pharmaceutical composition comprises one or more suitable preservatives. Non limiting examples of preservatives include benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid, hydrogen peroxide, the like and/or combinations thereof. A preservative can comprise a quaternary ammonium compound, such as benzalkonium chloride, benzoxonium chloride, benzethonium chloride, cetrimide, sepazonium chloride, cetylpyridinium chloride, or domiphen bromide (BRADOSOL®). A preservative can comprise an alkyl-mercury salt of thiosalicylic acid, such as thimerosal, phenylmercuric nitrate, phenylmercuric acetate or phenylmercuric borate. A preservative can comprise a paraben, such as methylparaben or propylparaben. A preservative can comprise an alcohol, such as chlorobutanol, benzyl alcohol or phenyl ethyl alcohol. A preservative can comprise a biguanide derivative, such as chlorohexidine or polyhexamethylene biguanide. A preservative can comprise sodium perborate, Attorney Docket No.022098-0583845 imidazolidinyl urea, and/or sorbic acid. A preservative can comprise stabilized oxychloro complexes, such as known and commercially available under the trade name PURITE®. A preservative can comprise polyglycol-polyamine condensation resins, such as known and commercially available under the trade name POLYQUART® from Henkel KGaA. A preservative can comprise stabilized hydrogen peroxide. A preservative can be benzalkonium chloride. In some embodiments a pharmaceutical composition is free of preservatives. [0079] In some embodiments a pharmaceutical composition is substantially free of serum proteins. In some embodiments a pharmaceutical composition is sterile. In some embodiments a pharmaceutical composition is lyophilized to a dry powder form, which is suitable for reconstitution with a suitable pharmaceutical solvent (e.g., water, saline, an isotonic buffer solution (e.g., PBS), and the like), which reconstituted form is suitable for parental administration (e.g., intravenous administration) to a mammal. [0080] The pharmaceutical compositions described herein may be configured for administration to a subject in any suitable form and/or amount according to the therapy in which they are employed. For example, a pharmaceutical composition configured for parenteral administration (e.g., by injection or infusion), may take the form of a suspension, solution or emulsion in an oily or aqueous vehicle and it may contain formulation agents, excipients, additives and/or diluents such as aqueous or non-aqueous solvents, co-solvents, suspending solutions, preservatives, stabilizing agents and or dispersing agents. In some embodiments a pharmaceutical composition suitable for parental administration may contain, in addition to an antigen binding agent and/or one or more anti-bacterial medications, one or more excipients. [0081] In certain embodiments, the primary vehicle or carrier in the pharmaceutical compositions described in the embodiments is an adjuvant. By “adjuvant” is meant one or more substances that cause stimulation of the immune system. In this context, an adjuvant is used to enhance an immune response to one or more vaccine antigens or antibodies. An adjuvant may be administered to a subject before, in combination with, or after administration of the vaccine or antibody. Examples of chemical compounds used as adjuvants include, but are not limited to, aluminum compounds (e.g., alum, Alhydrogel®), oils, block polymers, immune stimulating complexes, vitamins and minerals (e.g., vitamin E, vitamin A, selenium, and vitamin B12), Quil A (saponins), bacterial and fungal cell wall Attorney Docket No.022098-0583845 components (e.g., lipopolysaccarides, lipoproteins, and glycoproteins), hormones, cytokines, co-stimulatory factors, and cationic adjuvants based on liposomes formed by N,N′-dimethyl- N,N′-dioctadecylammonium (DDA) with the synthetic mycobacterial immunomodulator α,α′- trehalose 6,6′-dibeheneate (TDB) inserted into the lipid bilayer, known as CAF01. [0082] The compositions described in the embodiments can be useful as a vaccine. By “vaccine,” as used herein, is meant a composition that elicits an immune response in a subject to which it is administered. The mode of administration, dose, and number of administrations can be optimized by those skilled in the art in a known manner. By “vaccinate” or “vaccinating” as used herein, is meant to treat a mammal by administering a vaccine, e.g., to prevent or ameliorate a disease, pathological condition, disorder, or event. In some embodiments a vaccine comprises at least a Candida HYR1 polypeptide antigen, or an immunogenic fragment thereof, an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, and an acceptable adjuvant. In one embodiment, the vaccine comprises at least Hyr1p of SEQ ID NO: 1, Als3p of SEQ ID NO: 5, and an acceptable adjuvant. In another embodiment, the vaccine comprises at least an Hyr1p fragment of SEQ ID NO.: 4, an Als3p fragment of SEQ ID NO: 6, and CAF01. [0083] The compositions and vaccines described in the embodiments may be administered in combination with, or as an adjunctive therapy to antifungal drugs and/or antimicrobial drugs. The expressions “antifungal drug” or “antifungal drugs,” as used herein denote any known antifungal drug or drugs or those later discovered, and the embodiments are not limited to any specific antifungal drug. Suitable antifungal drugs include, for example, one or more of clotrimazole (Canesten), econazole, miconazole, terbinafine (Lamisil), fluconazole (Diflucan), ketoconazole (Daktarin), nystatin (Nystan), amphotericin, voriconazole, isavuconazole, echinocandins, posaconazole, flucytosine, itraconazole, caspofungin, griseofulvin, ravuconazole, anidulafungin, micafungin, ciclopirox, kerydin, and jublia. [0084] As used herein, the terms “antimicrobial agent” or “antimicrobial drug” or “antimicrobial(s)” are used to encompass materials, typically chemicals, which kill microbes or retard the growth of microbes to a statistically significant degree. These terms should be understood to include bactericides, fungicides, and other such agents. The terms “antimicrobial,, “bactericide,” and “fungicide” are well-known to those skilled in the art and Attorney Docket No.022098-0583845 their meanings will be readily discerned by the context in which each term is used. Suitable antimicrobial agents or antimicrobial drugs include, for example, one or more of an antibiotic such as Ceftazidime (a cephalosporin antibiotic), or an antibiotic selected from the group consisting of an aminoglycoside, an ansamycin, a carbacephem, a carbapenem, a cephalosporin, a glycopeptide, a lincosamide, a lipopeptide, a macrolide, a monobactam, a nitrofuran, a oxazolidonone, a penicillin, a polypeptide, a quinolone, a sulfonamide, a tetracycline, a chloramphenicol, a phosphonic acid antibiotic and a mycobacteria antibiotican. Suitable antimicrobial agents also include antifungal drug such as any of those mentioned previously, an antimicrobial agent such as Colistin (known as polymyxin E). [0085] The compositions and vaccines described in the embodiments may be either aqueous or non-aqueous in nature. For example, in certain embodiments, a suitable vehicle or carrier can be water for injection, physiological saline solution or artificial cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. In some embodiments, the saline comprises isotonic phosphate- buffered saline. In certain embodiments, neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. In certain embodiments, pharmaceutical compositions comprise Tris buffer of about pH 7.0 - 8.5, or acetate buffer of about pH 4.0 - 5.5, which can further include sorbitol or a suitable substitute therefore. In certain embodiments, a composition comprising an antigen binding agent, with or without at least one additional therapeutic agents, can be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents (Remington 's Pharmaceutical Sciences, supra) in the form of a lyophilized cake or an aqueous solution. Further, in certain embodiments, a composition or vaccine comprising an antigen binding agent, with or without at least one additional therapeutic agents, can be formulated as a lyophilized form (e.g., a lyophilized powder or crystalline form, a freeze dried form) using appropriate excipients such as sucrose. [0086] In some embodiments a carrier facilitates the incorporation of a compound into cells or tissues. For example dimethyl sulfoxide (DMSO) is a commonly utilized carrier as it facilitates the uptake of many organic compounds into the cells or tissues of an organism. In some embodiments, a pharmaceutical carrier for a composition described herein can be selected from castor oil, ethylene glycol, monobutyl ether, diethylene glycol monoethyl ether, Attorney Docket No.022098-0583845 corn oil, dimethyl sulfoxide, ethylene glycol, isopropanol, soybean oil, glycerin, zinc oxide, titanium dioxide, glycerin, butylene glycol, cetyl alcohol, and sodium hyaluronate. [0087] The compositions and/or vaccines described herein can include any suitable buffers, such as for example, sodium citrate buffer and/or sequestering agents, such as an EDTA sequestering agent. Ingredients, such as meglumine, may be added to adjust the pH of a composition or antigen binding agent described herein. Antigen binding agents and compositions described herein may comprise sodium and/or iodine, such as organically bound iodine. Compositions and compounds used herein may be provided in a container in which the air is replaced by another substance, such as nitrogen. [0088] In certain embodiments, the optimal pharmaceutical composition and/or vaccine will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format and desired dosage (see e.g., Remington's Pharmaceutical Sciences, supra). In certain embodiments, such compositions and/or vaccines may influence the physical state, stability, rate of in vivo release and rate of in vivo clearance of the antibodies of the invention. Administration and Formulation [0089] In some embodiments, compositions and vaccines described herein are used to prevent and/or treat a fungal infection or a fungal-bacterial mixed infection. In certain embodiments a composition or vaccine is administered to a subject at risk of acquiring a fungal infection or a fungal-bacterial mixed infection. A composition or vaccine that is used to prevent a fungal infection or a fungal-bacterial mixed infection is often administered to a subject at risk of acquiring a fungal infection or a fungal-bacterial mixed infection. In certain embodiments a method of preventing a fungal infection or a fungal-bacterial mixed infection comprises administering a composition or vaccine described herein prior to detection or diagnosis of a fungal infection or a fungal-bacterial mixed infection. Any suitable method of administering a pharmaceutical composition or vaccine to a subject can be used herein. [0090] The exact formulation and route of administration for a composition or vaccine for use according to the methods described herein can be chosen by the individual physician in view of the patient’s condition. See, e.g., Fingl et al.1975, in “The Pharmacological Basis of Therapeutics,” Ch.1, p.1; which is incorporated herein by reference in its entirety. Any Attorney Docket No.022098-0583845 suitable route of administration can be used for administration of a pharmaceutical composition or antigen binding agent described herein. Non-limiting examples of routes of administration include topical or local (e.g., transdermally or cutaneously, (e.g., on the skin or epidermus), in or on the eye, intranasally, transmucosally, in the ear, inside the ear (e.g., behind the ear drum)), enteral (e.g., delivered through the gastrointestinal tract, e.g., orally (e.g., as a tablet, capsule, granule, liquid, emulsification, lozenge, or combination thereof), sublingual, by gastric feeding tube, rectally, and the like), by parenteral administration (e.g., parenterally, e.g., intravenously, intra-arterially, intramuscularly, intraperitoneally, intradermally, subcutaneously, intracavity, intracranially, intra-articular, into a joint space, intracardiac (into the heart), intracavernous injection, intralesional (into a skin lesion), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intrauterine, intravaginal, intravesical infusion, intravitreal), the like or combinations thereof. [0091] In some embodiments a composition or vaccine herein is provided to a subject. A composition or vaccine that is provided to a subject is often provided to a subject for self- administration or for administration to a subject by another (e.g., a non-medical professional). For example a composition described herein can be provided as an instruction written by a medical practitioner that authorizes a patient to be provided a composition or treatment described herein (e.g., a prescription). In another example, a composition or vaccine can be provided to a subject where the subject self-administers a composition orally, intravenously or by way of an inhaler, for example. [0092] Compositions or vaccines for injection include sterile aqueous solutions (where water soluble) or dispersions and sterile powders (e.g., sterile lyophilized preparations) for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, NJ) or phosphate buffered saline (PBS). The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and polyethylene glycol), and suitable mixtures thereof. Fluidity can be maintained, for example, by the use of a coating such as lecithin, or by the use of surfactants. Antibacterial and anti-bacterial agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid and thimerosal. Including an agent that delays absorption, for example, aluminum monostearate and gelatin can prolonged absorption of injectable compositions. Attorney Docket No.022098-0583845 Polysorbate 20 and polysorbate 80 can be added into the formulation mixture, for example, up to 1%. Other non-limiting additives include histidine HCl, α,α-trehalose dehydrate. [0093] Alternately, one can administer compositions or vaccines for use according to the methods of the invention in a local rather than systemic manner, for example, via direct application to the skin, mucous membrane or region of interest for treating, including using a depot or sustained release formulation. [0094] The pharmaceutical compositions or vaccines can be manufactured by any suitable manner, including, e.g., by means of conventional mixing, dissolving, granulating, dragee- making, levigating, emulsifying, encapsulating, entrapping or tableting processes. [0095] Pharmaceutical compositions or vaccines for use herein thus can be formulated in any suitable manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation can depend upon the route of administration chosen. In particular, any suitable formulation, ingredient, excipient, the like or combinations thereof as listed in “Remington’s Pharmaceutical Sciences,” Mack Publishing Co., Easton, PA, 18th edition, 1990. can be used with a composition described herein. Any suitable techniques, carriers, and excipients can be used, including those understood in the art; e.g., in Remington’s Pharmaceutical Sciences, above, all pages of which are incorporated herein by reference in their entirety, including without limitation for all of the types of formulations, methods of making, etc. [0096] Some embodiments relate to methods of treating or preventing a gram negative bacterial infection through administration of compositions and/or vaccines described herein to the upper respiratory track/bronchi in a mammal in need thereof, for example, by contacting at least part of the upper respiratory tract/bronchi of a mammal with a therapeutically effective amount of a composition as described above or elsewhere herein. The composition and/or vaccine can be, for example, formulated as an aerosol formulation, including formulated for use in a nebulizer or an inhaler. The composition and/or vaccine further may include other pharmaceutically acceptable components such as a preservative. [0097] Compositions and/or vaccines for use according to the methods of the invention can be, in some embodiments, aerosolized compositions. The aerosolized composition can be Attorney Docket No.022098-0583845 formulated such that the composition has increased solubility and/or diffusivity. The composition and/or vaccine can comprise a carrier. A carrier can improve the absorption of the composition, change the viscosity of a composition, improve the solubility of the composition and/or vaccine, or improve the diffusivity of a composition compared to a pharmaceutical composition and/or vaccine that does not comprise a carrier. [0098] Liquid pharmaceutically administrable compositions and/or vaccines can, for example, be prepared by dissolving, dispersing, etc. an antigen binding agent as defined above and optional pharmaceutical adjuvants in a carrier (e.g., water, saline, aqueous dextrose, glycerol, glycols, ethanol or the like) to form a solution or suspension. Solutions to be aerosolized can be prepared in any suitable form, for example, either as liquid solutions or suspensions, as emulsions, or in solid forms suitable for dissolution or suspension in liquid prior to aerosol production and inhalation. [0099] For administration by inhalation, the compositions and/or vaccines described herein can conveniently be delivered in the form of an aerosol (e.g., through liquid nebulization, dry powder dispersion or meter-dose administration). The aerosol can be delivered from pressurized packs or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. Dosages and Products [00100] Certain embodiments provide pharmaceutical compositions and/or vaccines where the active ingredients are contained in an amount effective to achieve its intended purpose. A “therapeutically effective amount” means an amount sufficient to prevent, treat, reduce the severity of, delay the onset of or inhibit a symptom of a fungal infection or a fungal-bacterial mixed infection. The symptom can be a symptom already occurring or expected to occur. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. Attorney Docket No.022098-0583845 [00101] The term “an amount sufficient” as used herein refers to the amount or quantity of an active agent (e.g., an Hyr1 antigen and an Als3p antigen) present in a pharmaceutical composition that is determined high enough to prevent, treat, reduce the severity of, delay the onset of, or inhibit a symptom of a a fungal infection or a fungal-bacterial mixed infection and low enough to minimize unwanted adverse reactions. The exact amount of active agents or combination of active agents required will vary from subject to subject, depending on age, general condition of the subject, the severity of the condition being treated, and the particular combination of drugs administered. Thus, it is not always possible to specify an exact universal amount sufficient to prevent or treat a gram negative bacterial infection for a diverse group of subjects. As is well known, the specific dosage for a given patient under specific conditions and for a specific disease will routinely vary, but determination of the optimum amount in each case can readily be accomplished by simple routine procedures. Thus, an appropriate “an amount sufficient” to prevent or treat a gram negative bacterial infection in any individual case may be determined by one of ordinary skill in the art using routine experimentation. [00102] In other embodiments, a therapeutically effective amount can describe the amount necessary for a significant quantity of the composition to contact the desired region or tissue where prevention or treatment of a fungal infection or a fungal-bacterial mixed infection is desired. [00103] The antigens Hyr1 and Als3p described herein can be administered at a suitable dose, e.g., at a suitable volume and concentration depending on the route of administration, and in suitable ratios of actives. Within certain embodiments, dosages of administered antigens can be from .01 mg/kg (e.g., per kg body weight of a subject) to 500 mg/kg, 0.1 mg/kg to 500 mg/kg, 0.1 mg/kg to 400 mg/kg, 0.1 mg/kg to 300 mg/kg, 0.1 mg/kg to 200 mg/kg, 0.1 mg/kg to 150 mg/kg, 0.1 mg/kg to 100 mg/kg, 0.1 mg/kg to 75 mg/kg, 0.1 mg/kg to 50 mg/kg, 0.1 mg/kg to 25 mg/kg, 0.1 mg/kg to 10 mg/kg, 0.1 mg/kg to 5 mg/kg or 0.1 mg/kg to 1 mg/kg. In some aspects the amount of an antigen binding agent can be about 10 mg/kg, 9 mg/kg, 8 mg/kg, 7 mg/kg, 6 mg/kg, 5 mg/kg, 4 mg/kg, 3 mg/kg, 2 mg/kg, 1 mg/kg, 0.9 mg/kg, 0.8 mg/kg, 0.7 mg/kg, 0.6 mg/kg, 0.5 mg/kg, 0.4 mg/kg, 0.3 mg/kg, 0.2 mg/kg, or 0.1 mg/kg. In some embodiments a therapeutically effective amount of an antigen binding agent is between about 0.1 mg/kg to 500 mg/kg, or between about 1 mg/kg and about 300 mg/kg. Volumes suitable for intravenous administration are well known. Attorney Docket No.022098-0583845 [00104] In some embodiments, the ratio of Hyr1 antigen to Als3p antigen ranges from about 10:1 to about 0.1:1, or from 9:1 to 0.5:1, or from 8:1 to 0.7:1, or from 5:1 to 0.9:1, or from 3:1 to 1:1, and any value or ratio therebetween. [00105] The compositions and/or vaccines can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the active ingredient. The pack can for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device can be accompanied by instructions for administration. The pack or dispenser can also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, can be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions and/or vaccines formulated in a compatible pharmaceutical carrier can also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Kits [00106] In some embodiments the compositions, formulations, combination products, vaccines, and materials described herein can be included as part of kits, which kits can include one or more of pharmaceutical compositions, antigen binding agents, and formulations of the same, combination drugs and products and other materials described herein. In certain embodiments a kit is a diagnostic kit comprising one or more antigen binding agents described herein. In some embodiments the products, compositions, kits, formulations, etc. can come in an amount, package, product format with enough medication to treat a patient for 1 day to 1 year, 1 day to 180 days, 1 day to 120 days, 1 day to 90 days, 1 day to 60 days, 1 day to 30 days, or any day or number of days there between, 1-4 hours, 1-12 hours, or 1-24 hours. [00107] The embodiments provide kits including pharmaceutical compositions and/or vaccines,, combination compositions and pharmaceutical formulations thereof, packaged into suitable packaging material. A kit optionally includes a label or packaging insert including a Attorney Docket No.022098-0583845 description of the components or instructions for use in vitro, in vivo, or ex vivo, of the components therein. Exemplary instructions include instructions for a diagnostic method, treatment protocol or therapeutic regimen. [00108] A kit can contain a collection of such components, e.g., two or more conjugates alone, or in combination with another therapeutically useful composition (e.g., an anti- proliferative or immune-enhancing drug). The term “packaging material” refers to a physical structure housing the components of the kit. The packaging material can maintain the components sterilely, and can be made of material commonly used for such purposes (e.g., paper, corrugated fiber, glass, plastic, foil, ampules, vials, tubes, etc.). [00109] Kits can include labels or inserts. Labels or inserts include “printed matter,” e.g., paper or cardboard, or separate or affixed to a component, a kit or packing material (e.g., a box), or attached to an ampule, tube or vial containing a kit component. Labels or inserts can additionally include a computer readable medium, optical disk such as CD- or DVD- ROM/RAM, DVD, MP3, magnetic tape, or an electrical storage media such as RAM and ROM or hybrids of these such as magnetic/optical storage media, FLASH media or memory type cards. [00110] Labels or inserts can include identifying information of one or more components therein, dose amounts, clinical pharmacology of the active ingredient(s) including mechanism of action, pharmacokinetics (PK) and pharmacodynamics (PD). Labels or inserts can include information identifying manufacturer information, lot numbers, manufacturer location and date. [00111] Labels or inserts can include information on a condition, disorder, disease or symptom for which a kit component may be used. Labels or inserts can include instructions for the clinician or for a subject for using one or more of the kit components in a method, treatment protocol or therapeutic regimen. Instructions can include dosage amounts, frequency or duration, and instructions for practicing any of the methods, treatment protocols or therapeutic regimes set forth herein. Kits of the invention therefore can additionally include labels or instructions for practicing any of the methods and uses of the invention described herein. Attorney Docket No.022098-0583845 [00112] Labels or inserts can include information on any benefit that a component may provide, such as a prophylactic or therapeutic benefit. Labels or inserts can include information on potential adverse side effects, such as warnings to the subject or clinician regarding situations where it would not be appropriate to use a particular composition. Adverse side effects could also occur when the subject has, will be or is currently taking one or more other medications that may be incompatible with the composition, or the subject has, will be or is currently undergoing another treatment protocol or therapeutic regimen which would be incompatible with the composition and, therefore, instructions could include information regarding such incompatibilities. [00113] Kits can additionally include other components. Each component of the kit can be enclosed within an individual container and all of the various containers can be within a single package. Invention kits can be designed for cold storage. Invention kits can further be designed to contain host cells expressing antibodies or antigen binding agents, or that contain nucleic acids encoding antibodies or antigen binding agents. The cells in the kit can be maintained under appropriate storage conditions until the cells are ready to be used. For example, a kit including one or more cells can contain appropriate cell storage medium so that the cells can be thawed and grown. [00114] Such diagnostic methods and kits can take any suitable form. For example, a kit can comprise or consist of a stick test, including necessary reagents to perform the method of the invention and to produce, for example, a colorimetric result which can be compared against a color chart or standard curve. Such kits can also comprise, e.g., a buffering agent, a preservative, or a protein stabilizing agent. A kit can also contain a control sample and/or a series of control samples (e.g., controls containing known amounts of fungal infections, e.g., a standard curve) which can be assayed and compared to the test sample contained. In some embodiments, each component of the kit is usually enclosed within an individual container, and all of the various containers are within a single package, along with instructions for determining whether the subject from which the sample is derived is suffering from or is at risk of developing a fungal infection or a fungal-bacterial mixed infection. [00115] The present applicant’s vaccine development program builds upon over 30 years of research in the immunology and pathogenesis of Candida albicans, which culminated in the characterization of Agglutinin-like sequence-3 protein (Als3, an adhesin and invasin factor for host tissues) and Hyphal regulated protein (Hyr1, a neutrophil evading factor). A Attorney Docket No.022098-0583845 recombinant Als3-based alum-adjuvanted (NDV-3A) vaccine and a recombinant Hyr1-based vaccine elicits robust T- and B-cell responses and protected against murine C. albicans hematogenoulsy disseminated candidiasis (including non-albicans spp.) and vulvovaginal candidiasis. The recombinant Als3p antigen adjuvanted in Alhydrogel® (NDV-3A) was investigated under IND in a Phase 1b/2a trial, demonstrating safety, immunogenicity and efficacy in protecting women <40 years of age with history of recurrent vulvovaginal candidiasis (RVVC) due to C. albicans from relapse for up to 12 months when vaccinated with a single dose, as shown in FIG.1. [00116] Bioinformatic and immune-profiling studies performed by the applicant has identified three Als3 orthologs on the C. auris cell wall with remarkable sequence and 3- dimensional (3-D) structural and functional similarity with C. albicans Als3p. Antibodies against C. albicans Als3p not only bind to C. auris, but also prevent biofilm formation and enhance the opsonophagocytic activity of macrophages. Importantly, NDV-3A vaccination significantly protected mice from a lethal hematogenously disseminated C. auris infection compared to placebo and yielded 10-fold lower fungal burden in primary target organs. Further, anti-Als3p serum antibodies recognize multiple strains of C. auris, belonging to all different clades. C. auris also have 8 orthologs of Hyr1p, out of which three proteins are present in all four clades of C. auris. These Hyr1-orthologs have high predicted structural similarity with Hyr1p and contain a central adhesive domain, N-terminal substrate-binding domain, and GPI-anchor (like Hyr1p). Anti-Hyr1 monoclonal antibodies raised by the applicant and others, bind to the C. auris surface and protect mice from C. auris disseminated infection, as shown in FIG.2. [00117] Different pathogens share similar medical settings and rely on similar strategies to cause disease (e.g., adhesion, biofilm formation, and iron uptake). Using computational modeling and bioinformatics, applicant has shown that Hyr1p also shares striking 3-D structural homology with the conserved hemagglutinin/hemolysin (FhaB) of AB and CPKP. Thus, C. albicans Hyr1p is a cross-kingdom antigen capable of inducing heterologous immunity against these gram-negative bacteria through active or passive vaccination (using mAB targeting the shared epitope). Initial proof-of-concept studies have shown that Hyr1 antigen-based active and passive immunization strategies protect against Gram-negative bacterial infections in murine models of disease, as shown in FIG.2. Attorney Docket No.022098-0583845 [00118] The applicant set out to develop a dual antigen-based cross-kingdom vaccine targeting multiple HAIs caused by C. albicans, C. auris, and Gram-negative bacteria (AB, KP, and PA). The inventors discovered an antigen-based vaccine combination of a C. albicans Als3p and Hyr1p, identified through a rigorous adjuvant and formulation screen in in vivo (see examples below). In a particular embodiment, the dual antigen vaccine, (referred to as VXV-01) comprises recombinant Als3p and Hyr1p, formulated in PBS and adjuvanted with an adjuvant that in some specific embodiments, is a two-component adjuvant system that consists of an immunomodulator and a cationic liposome, known as CAF01. The inventors surprisingly discovered that a dual antigen vaccine, referred to as VXV-01, comprising combinations of SEQ ID NOs: 1 and 5, or combinations of SEQ ID NOs: 4 and 6, with a two-component adjuvant system that includes an immunomodulator and a cationic liposome, known as CAF01, provided synergistic effects in targeting multiple HAIs caused by C. albicans, C. auris, and Gram-negative bacteria (AB, KP, and PA). EXAMPLES [00119] The following examples include detailed description of the chemistry involved, the various testing carried out by the inventors to determine a suitable composition, and proposed pharmacology/toxicology and clinical studies for the compositions described herein.

Attorney Docket No.022098-0583845 Example 1 – Chemistry, Manufacturing, and Controls [00120] Chemicals were non-GMP materials used in nonclinical studies, subcontracted through Biodextris. Manufacturing activities (for both antigens), which included upstream and downstream process development (Fig.11), a lab-scale confirmation run, non-GMP tox lot production at 1/10^th scale (stability studies currently ongoing), analytical methods transfer, and establishment as fit for purpose, vaccine formulation assay screening, and an in-use stability study to support dose preparation hold times for the toxicology study. [00121] As previously discussed, the Als3 antigen is a recombinant N-terminal region of an adhesin protein from C. albicans expressed in a Saccharomyces cerevisiae, and may include SEQ ID NOs: 5 and 6. Hyr1 constitutes a recombinant N-terminal portion of the native cell surface protein from C. albicans, that is expressed in an insoluble inclusion body form in E. coli, and may include SEQ ID NOs: 1, 3, and 4. Als3 Drug Substance Manufacturing [00122] The S. cerevisiae strain FY03-1, maintaining the vector pTEF1-S1Als3-2, was initially established as a Master Cell Bank (MCB) by Althea Technologies, utilizing the parent strain DY150 sourced from Clontech. Subsequent developmental efforts at the University of Nebraska-Lincoln (UNL) led to a Research Cell Bank (RCB) designated as Fy03-1/2um-full/TEF1p which aimed to better stabilize the cell line through inclusion of the full 2µm origin sequence. Biodextris, building upon the UNL RCB, established a Working Research Cell Bank (WRCB) and conducted media optimization processes to enhance the growth and stability of the FY03-1 strain. The drug substance for toxicology studies was manufactured under non-GMP conditions in a 10L bioreactor scale with upstream (USP) and downstream processes (DSP) applicable for S. cerevisiae cell line and protein purification and monitored via preliminary in-process controls and tests. The upstream and downstream processes are shown in Figure 11. A GMP Master Cell Bank is currently being produced by the Preclinical Service Contract mechanism and is being used to support GMP production to supply the Phase 1 clinical material, which will include a full release test panel as well as characterization analysis against the established RCB. Attorney Docket No.022098-0583845 Hyr1 Drug Substance Manufacturing [00123] In 2013, Nature Technologies Inc. (NTC) began the creation of a cell line to express recombinant Hyr1 via a BL21 Competent Escherichia coli stock from New England Biolabs and the gene insert provided by GeneScript. NTC performed ligation of the gene insert into its proprietary expression vector. Briefly, following creation the plasmid was transformed into the BL21 Competent E. coli cell line and underwent rounds of culture and clonal isolation to screen for promoter regulation, productivity, copy number, restriction map, and level of dimerization, resulting in selection of a colony to establish the pre‐RCB cell bank. In addition to the testing performed to identify the banking candidate, one vial of the pre‐RCB stock was taken into a 10‐liter fermentation to determine the suitability of the selected clone for production of Hyr1, as well as plasmid stability at the end of fermentation. [00124] The drug substance (DS) intended for toxicology studies contained the N-terminal regions of Als3p (18-450 amino acids – SEQ ID NO: 6) and Hyr1p (154-350 amino acids – SEQ ID NO: 4). These sequences were expressed in Saccharomyces cerevisiae FY03-1 strain and Escherichia coli BL21 strain, respectively. For Als3p manufacturing, a previously developed Research Cell Bank (RCB) was used to establish a Working Research Cell Bank (WRCB) and to conduct media optimization processes to enhance the growth and stability of the strain (Figure 11). For Hyr1p manufacturing, a vial of pre‐RCB stock was expanded into a 10‐liter fermentation to determine the suitability of the selected clone for producing Hyr1 and plasmid stability at the end of fermentation. Finally, Als3p and Hyr1p were manufactured under non-GMP conditions in a 10L bioreactor scale with upstream (USP) and downstream processes (DSP) applicable for S. cerevisiae and E. coli cell lines, respectively. The manufacturing and protein purification processes were monitored via preliminary in-process controls and tests shown in Figure 11 and Table 1 below. The purity and integrity of both Als3p and Hyr1p were verified by SDS-PAGE analysis. The purified antigens produced in GLP-compliant conditions were filled in vials and stored at -80^oC. Table 1. Test methods for Drug Substance lot release and stability assessment. Attribute Antigen Parameter Method Provisional Used for Specifications Stability Program Safety Als3, Hyr1 Endotoxin Kinetic chromogenic LAL < 1000 EU/mg X assay Safety Als3, Hyr1 Microbial Limits USP<61> < 1 CFU/ml X Attorney Docket No.022098-0583845 Safety Als3, Hyr1 Residual Method not yet developed Not yet defined - antifoam Quality Als3, Hyr1 pH USP <791> 7.0 ± 0.3 X Quality Als3, Hyr1 Appearance Method based on USP <631> Clear, colorless liquid (< X USP standard A, comparable to water). Essentially free of visible particles Identity/ Als3, Hyr1 Protein Identity/ SDS-PAGE and Western Blot Relative purity: ≥ 95%. X Purity Protein Size Variants Profile: Report Results Identity/ Als3, Hyr1 Protein Identity/ SDS-PAGE and Western Blot Identity: Positive. X Purity Protein Size Variants Profile: Report Results Strength Als3, Hyr1 Protein Content UV Spectrophotometry 1.5 ± 0.3 mg/ml X Purity Als3, Hyr1 Protein Charge Isoelectric Point Report results (pI) X Variants Determination by cIEF Safety Als3 Residual Benzonase Method developed at Not yet defined - Biodextris Quality Als3, Hyr1 Particle Size Variants SEC-UV ≥ 90% monomer X Potency Als3 Immuno-potency Quantitative Sandwich ELISA 50 – 150% of reference X Potency Hyr1 Immuno-potency Evaluation of Mouse Immune 50 – 150% of reference X Serum by Indirect ELISA Safety Als3 Host cell DNA PicoGreen™ dsDNA Assay < 500 ng/ml - Safety Als3 Host cell proteins ELISA Report results - Safety Hyr1 Host cell DNA qPCR < 500 ng/ml - Impurity Hyr1 Host-cell proteins ELISA < 2000 ng/ml - Purity Als3 Carbohydrates RP-HPLC ≤ 10% X Purity Als3 Carbohydrates HPLC Report results X Description and Composition of Drug Product [00125] The final formulated (Als3+Hyr1+CAF01 adjuvant) vaccine product was comprised of two separately purified recombinant antigens, SEQ ID NOs: 4 and 6,combined with 3 mg/mL of a two-component liposomal adjuvant system (CAF01; Croda International LLC) intended for IM administration. Formulation development for the combined Als3 and Hyr1 antigens of SEQ ID NOs: 4 and 6, and CAF01 adjuvant in a final formulated format is included above. The array of lot release tests performed on each lot of DP is shown in Table 2. Table 2. Test methods for Drug Product lot release and stability assessment. To be To b Used for Attribute Parameter Method e developed qualified Stability Program Quality Appearance USP<631> X X Quality pH USP <791> X Quality Osmolality USP <785> - Purity Protein profile SDS PAGE-reduced and non-reduced X X X Attorney Docket No.022098-0583845 Identity Identity/profile Western Blot X X X Strength Protein concentration UV-Vis X X X Purity Protein profile cIEF X X X Purity Protein profile HPLC-SEC X X X Potency ELISA signal (Als3) ELISA X X X Potency ELISA signal (Hyr1) ELISA X X X Purity/Identity DDA analysis (Adjuvant) HPLC-MS X X X Purity/Identity TDB analysis (Adjuvant) HPLC-CAD X X X Potency Macrophage activation test (Adjuvant) ELISA potency X X X Quality Size and polydispersity assay (Adjuvant) DLS X X X Safety Endotoxins LAL X X X Sterility Sterility USP<71> X - Safety Container Closure Integrity CCIT X X X Example 2 – Adjuvant and Vaccine Candidate Selection [00126] The following techniques were carried out to determine appropriate antigens for use herein, as well as suitable adjuvants. [00127] Several adjuvants were acquired for vaccine formulation optimization: Alhydrogel (aluminum hydroxide alum), beta-Glucan Chitosan Particle (GCP), Cation Adjuvant Formulation-01 (CAF01), MF-59, Asgipan (Saponin Adjuvant) BDX100, and BDX300. These adjuvants were combined with 0, 3, 10, and 30 µg/dose of Als3 (SEQ ID NO: 6) with each of 0, 1, 3, 10, or 30 µg /dose of Hyr1 (SEQ ID NO: 4). Alum formulations were used as a comparator for other adjuvant formulations. Encapsulation of Als3p and Hyr1p antigens in GCP were confirmed by SDS-PAGE. The immunogenicity of each antigen + adjuvant vaccine formulation was determined by vaccinating 4- to 6-week-old CD-1 mice (n=5 mice/group) on days 0 and 21 subcutaneous (SC) (intranasal [IN] for BDX100 and BDX300 formulations). Mice were euthanized two weeks after the final vaccination, and sera and spleens collected. Sera were used to evaluate anti-Als3 and Hyr1 IgG antibody endpoint titers by ELISA. Splenocytes were used for FluroSpot assay to determine the frequency of Als3 or Hyr1 antigen specific Th1, Th2, or Th17 cell and the top vaccine formulations were shortlisted based on immunogenicity profiles. The antigen ratio in these formulations was 10 or 30 µg/dose of Als3 mixed with either 3, 10, or 30 µg/dose of Hyr1. Monovalent vaccine formulations with either Als3 (SEQ ID NO: 6) or Hyr1 (SEQ ID NO: 4) alone were used to compare antibody and T cell development to dual antigen formulations and any potential immunodominance by one antigen over the other. [00128] Dual antigen formulations (10/3, 10/10, 10/30, 30/3, 30/10 and 30/30) induced high antibody levels and measurable Th1/Th2/Th17 immune responses. The Alhydrogel (alum) formulations induced robust anti-Als3 and anti-Hyr1 IgG antibodies. The anti-Hyr1 antibody Attorney Docket No.022098-0583845 titers were higher compared to anti-Als3 IgG titers (FIG.3). In addition, anti-Als3 IgG titers were not influenced negatively by increasing the Hyr1 antigen dose in the vaccine formulation. Therefore, Als3 and Hyr1 antigens are not antagonistic to each other. [00129] Alum formulations did not induce detectable T-cell responses. MF59 formulations induced high antibody titers to both antigens and a robust Th2 (IL-4) response but poor Th1 (IFN-γ) and Th17 (IL-17) immune responses (data not shown). CAF01 formulations induced antibody titers to both antigens comparable to the alum data. Importantly, CAF01 also induced a robust and balanced T-cell response against both Als3 (SEQ ID NO: 6) and Hyr1 (SQ ID NO: 4) antigens at high antigen doses, represented by Th1, Th2, and Th17 cells, as shown in FIG.4. Figure 14A shows the efficacy of different adjuvant vaccine formulations against C. albicans, and Figure 14B shows the efficacy of different adjuvant vaccine formulations against C. auris. [00130] All adjuvant formulations induced robust IgG antibody titers and depended on the adjuvant used and not on the antigen ratio in the vaccine formulations. GCP vaccine formulations induced the highest anti-Als3p IgG antibody titers, followed by MF59, Alum and CAF01, BDX100, and BDX300. Anti-Hyr1p IgG titers were the highest for the Alum formulations, followed by CAF01, BDX100, BDX300, and MF59 adjuvant formulations. Relative antigen dosage in the vaccine formulations did not influence the Als3p and Hyr1p antigen-specific titers in any adjuvant except the CAF01 adjuvant, which shows reduced Anti-Als3p IgG titters with high Hyr1p doses in the vaccine formulation. Furthermore, the dual vaccine formulations induced similar or higher Als3p or Hyr1p mono-antigen vaccine formulations and did not change with the antigen dosage in the vaccine formulation. Thus, anti-Als3p or Hyr1p-specific IgG titers were not negatively influenced by increasing the relative Hyr1 or Als3p antigen dose in the vaccine formulation. Therefore, the Al3p and Hyr1p antigens are not antagonistic to each other in the dual antigen vaccine formulations. Alum Hyr1p mono-antigen formulation at 10 µg/dose induced higher anti-Hyr1p IgG titer compared to both CAF01 and BDX100 adjuvant formulations. Moreover, CAF01 and BDX100 adjuvant formulations showed an antigen dose-dependent increase in anti-Hyr1p IgG titers, which became similar to Alum mono-Hyr1 antigen formulations at 30µg/dose, indicating more antigen dose dependency with these adjuvants. For CAF01 adjuvant formulations, this antigen dose dependency is less strong than BDX100. Overall, anti-Hyr1p IgG titers were higher than anti-Als3p IgG titers in adjuvant formulations, including alum, Attorney Docket No.022098-0583845 MF59, CAF01 (except in formulations with 10 µg Hyr1p antigen dosage), BDX100 and BDX300 adjuvant formulations, and this trend did not change with increasing Als3p antigen relative to Hyr1p antigen dosage. In GCP vaccine formulations, this trend was reversed, showing higher anti-Als3p IgG titers compared to anti-Hyr1p IgG at all Als3p/Hyr1p antigen ratios. [00131] The T cell immune responses in the splenocytes also were evaluated using a triple color IFN-g (Th1), IL4 (Th2), and IL17(Th17) FluroSpot assay. Alum-based vaccine formulations failed to elicit CD4+ T cell responses, while all other vaccine formulations induced detectable Th1, Th4, and Th17 immune responses. Among these, CAF01 formulations generated robust and balanced Th1, Th4, and Th17 immune responses in a vaccine antigen dosage-dependent manner, targeting both Als3p and Hyr1p antigens. BDX100 formulations predominantly elicited Th1-biased responses, with equal targeting of Als3p and Hyr1p antigens, whereas BDX300 induced balanced Th1, Th4, and Th17 responses that were proportionally equivalent but of lower magnitude compared to CAF01. A notable difference between BDX100 and BDX300 was the stronger Th1 response observed with BDX100, although their Th2 and Th17 responses were comparable. GCP formulations elicited strong Th1- and Th17-skewed immune responses, favoring the Als3p antigen. In contrast, MF59-based formulations generated weak Th1, Th2, and Th17 responses regardless of the Als3p and Hyr1p antigen dosage. Overall, CAF01, BDX100, and BDX300 formulations produced proportionally similar Th1, Th4, and Th17 responses specific to Als3p and Hyr1p, with the magnitude of responses generally dependent on antigen dosage, except for BDX300. Efficacy of Selected Vaccine Formulations in Mouse Infection Models [00132] Based on the immunogenicity profile, the efficacy of 10µg/30µg and 30µg/30µg doses adjuvanted with CAF01 against primary target pathogens C. albicans and C. auris was investigated. Briefly, CD-1 mice (n ≥10/group) were vaccinated SC and received booster immunizations on day 21 or on day 21 and 35. Fourteen days after the final boost, mice were infected intravenously (IV) with C. albicans (SC5314 strain) or C. auris (CAU09 strain). For C. auris infection, mice were immunosuppressed on day -2 relative to infection using 200 mg/kg cyclophosphamide (intraperitoneal, IP) and 250 mg/kg cortisone acetate given SC. For GNB infection, an additional dose of immunosuppression drugs was administered on day +3, relative to infection with either AB (HUMC1 strain, inhalation infection), KP (KP-RM strain, Attorney Docket No.022098-0583845 or PA (PA01 strain, intratracheal infection). Mice were monitored for survival for 21 days post-infection or sacrificed 4 days post-infection for tissue microbial burden determination, as shown in FIG.5. Among all the adjuvant formulations tested, only CAF01 and BDX100 vaccine formulations showed significant protection against both hematogenously disseminated C. albicans and C. auris infections with 36 to 42% survival (12-14 days of MST) vs the placebo group show ing 0% survi val (8-11 days of M ST). Additiona l vaccination studies comparing CAF01 and BDX100 adjuvant vaccine formulations revealed that CAF01 formulations, specifically Als3p/Hyr1p: 30µg/10µg, 10µg/10µg afforded superior protective efficacies to BDX100 formu la ti ons a gai nst C. alb icans and C. auris dissemi nated infection after two boosters and one booster vaccination, respectively. Based on initial efficacy studies, CAF01 adjuvant vaccine formulations with 30µg/10µg, 10µg/10µg and 30µg/3µg of Als3/Hyr1 (SEQ ID NO: 6/SEQ ID NO:4) antigen ratios were prioritized. Table 3 shows the results of these efficacy studies: Efficacy against C. albicans and C. auris [00133] In the C. albicans model, the three-dose schedule was significantly protective compared to two vaccine doses (only three dose data is shown). Briefly, the each of the 30µg/10µg, 10µg/10µg and 10µg/10µg of Als3/Hyr1(SEQ ID NO: 6/SEQ ID NO:4) antigen ratios showed ~40-45% survival with >15 days of median survival time vs.0% survival with 10.0 days of MST in the placebo group (Table 3 and Figure 6). [00134] For C. auris, the two-dose schedule was enough to provide significant protection, and a third vaccination did not improve efficacy (only two-dose data is shown in Table 1 and Attorney Docket No.022098-0583845 Figure 6). Immunization with the CAF01 vaccine formulations resulted in 30-55% survival with >14-21 days of mean survival time (MST) vs.0% survival and 10 days of median survival time (MST) in the placebo mice (CAF01 vaccinated without Als3 (SEQ ID NO: 6) or Hyr1 (SEQ ID NO:4)). Similar results were seen when animals were challenged as late as 15 weeks after final vaccination. Efficacy against Gram (-) bacterial pneumonia [00135] Two vaccine doses (One booster immunization) provided significant protection against gram negative bacterial (GNB) infections, and additional booster immunization did not improve survival efficacies. Table 3 and Figure 6 show one boost data for GNB infections . A. baumannii. CAF01 formulations 30/10 and 10/10 were significantly protected with 40% (14 days of MST, p=0.017) and 45% (15 days of MST, p=0.002) against AB (vs placebo mice with 0% survival and 8 days of MST), respectively. K. pneumoniae. CAF01 formulations 30/10, 10/10, and 30/3 showed significantly higher survival efficacies of 60% (>21 days of MST, p=0.003), 50% (19 days of MST, p=0.017), and 50% (>21 days of MST, p=0.005), against KP vs.15% survival in the placebo group, respectively. P. aeruginosa. CAF01 vaccine formulations 30/10, 10/10, and 30/3 were significantly protective against PA but had poor survival efficacies of 10% (5 days of MST), 30% (5 days of MST), and 0% (6 days of MST), respectively vs 0% (2 days of MST) in placebo group. Evaluation of Weight Loss and Tissue Microbial Burden in Vaccinated Mice [00136] The top protective vaccine formulations containing CAF01 against target pathogens 10µg/10µg and 30µg/10µg were further tested by comparison of the weight loss and tissue microbial burden in the target organs of vaccinated and placebo mice. For, C. albicans, three vaccine doses were given at days 0, 21 and 35. For other infections, two vaccine doses were given at days 0 and 21. Tissue pathogen burden in target organs of mice (Kidney for C. albicans, C. auris and AB; Lung for AB, Heart and Brain for C. auris, Vagina for C. albicans) Attorney Docket No.022098-0583845 were evaluated after 4 post-infection. Both 30µg/10µg and 10µg/10µg vaccine formulations prevented significant weight loss compared to the placebo group in infected mice (Figure 7). [00137] In addition, both the 30µg/10µg and 10µg/10µg vaccine formulations significantly reduced tissue microbial burden in the target organs, compared to the placebo group (Figure 8). In conjunction with mouse survival data and tissue microbial burden data, it was concluded that a 10µg/10µg formulation showed consistent efficacy (data from >3 independent experiments) against all the target pathogens. Further experiments were performed with this formulation. Mechanism of Vaccine-Mediated Protection [00138] To investigate the mechanism of vaccine-mediated protection, passive transfer and CD4 T cell depletion experiments were conducted as previously described. For the passive transfer experiment, sera from vaccinated mice were administered intraperitoneally to the immunosuppressed, naïve infected mice on days 0 and 7 relative to the infection. For C. auris and A. baumannii the mice were immunosuppressed as described earlier. Transfer of sera significantly protected mice against C. auris and AB infection but not against C. albicans (Figure 9, left panel). In the CD4 T cell depletion experiment, the mice were vaccinated with the CAF0110µg/10µg vaccine or placebo (n=10 mice/group) on days 0, 21. After the vaccination, both vaccine and placebo mice were split into CD4 depletion and no depletion sub-groups. For the depletion groups, CD4 T cells were depleted by anti-CD4 antibody intraperitoneal injections on days -3 and 0 relative to infection. All mice were immunosuppressed (as described previously) prior to being infected with C. auris, 14 days following the final vaccination. Vaccination mice with their CD4 T cells intact survival efficacy of 40%, 30%, and 50% against C. albicans, C. auris and A. baumannii, which was reduced to 20%, 0%, and 40%, respectively, after the CD4 T cell depletion (Figure 9). These data suggest that vaccine-mediated protection against these target pathogens depends partially on antibodies and significantly on CD4 T cells. Durability of Vaccine-Induced Immunity [00139] To investigate for the durability of immunity afforded by the vaccine, the antigen- specific antibody and T-cell responses were monitored at different time points and over 270 days following immunization with either 10µg/10µg vaccine formulation given twice (days 0, Attorney Docket No.022098-0583845 and 21) or thrice (days 0, 21, and 35). After the final booster vaccination, mice were euthanized on days 14, 28, 90, 180, or 270 to evaluate antibody titers, T cell immune responses by ELISA, and FluroSpot assay, respectively. The mice vaccinated with the 10µg/10µg formulation showed robust antibody responses against Als3 (SEQ ID NO: 6) and Hyr1 (SEQ ID NO: 4) antigens on day 14, which did not wane for up to 9 months. The three- dose series induced ~1 log higher IgG antibody titer than the two-dose series. After one booster immunization, Als3 and Hyr1-specific T-cell responses were similar in magnitude but biased towards Th1 and Th2, which also declined after two weeks but maintained for 9 months. Two booster immunizations induced similar Th1 immune responses against both Als3 and Hyr1 antigens, but the Th2 immune response was biased towards Als3. Further, the magnitude of T-cell development peaked at day 14 for one booster immunization and at day 28 for the two booster immunizations. Finally, two booster immunizations induced significantly higher antigen specific Th2 immune response than one booster immunization (Figure 10). These results are consistent with an efficacy experiment where mice were challenged 15 weeks following the boost which showed a 30% 21-day survival vs.0% for placebo and 14 days MST for vaccinated vs.9 days for placebo (p=0.0063, n=10 mice per group) (data not shown). Vaccine Efficacy in Combination with Anti-Microbial Drugs [00140] The efficacy of the CAF0110/10 (SEQ ID NO: 6/SEQ ID NO:4) vaccine formulation was evaluated in combination with a sub-protective dose of antimicrobial drugs in animal models with target pathogens. Briefly, mice were vaccinated as above, and two weeks after the vaccination, the mice were infected with the target pathogen. The treatment with a suboptimal dose of the antimicrobial drug started on day +1 post-infection. The inventors discovered that drug treatment enhanced survival efficacies (15 – 35% survival increase) and median survival times (>4-16 days) compared to either drug or vaccine alone. However, we did not see a statistically significant difference between vaccine alone vs drug + vaccine combination. See Table 4 below: Attorney Docket No.022098-0583845 TABLE 4. CAF0110^g/10^g vaccine efficacy in combination with antimicrobial drugs. Infection N Placebo Drug Only 10/10 10/10 + Drug Treatment Model % Survival (Median Survival days) C. albicans 10 0% (10.5) 30% (14.5)* 30% (14)* 50% (17.5)* Fluconazole (0.5 mg/kg from days 1 to 5 orally) C. auris 10 0% (3) 0% (4.5) 30% (7.5)* 50% (17.5)* Micafungin (2.5 mg/kg from days 1 to 7 IP once daily) A. baumannii 20 0% (12.5) 30% (13) 40% (16)* 55.5% (>21)* Colistin (2.5 mg/kg from days 1 to 7 through IP twice daily) P. aeruginosa 10 0% (2.5) 40% (4)* 35% (4.5)* 70% (>21)* Ceftazidime (125 mg/kg from days 1 to 7 through IP once daily) [00141] CAF01 vaccine formulations induced strong antibody and T cell immune responses, and selected CAF01 formulations also show protective efficacies against target pathogens. CAF0130µg /10µg and 10µg /10µg (Als3p/Hyr1p (SEQ ID NO: 6/SEQ ID NO:4)) vaccine formulations protected significantly against all five infections with ~ 50% survival efficacies (vs. ~ 0% for placebo) and longer median survival time across all targeted pathogens compared to other formulations. A comprehensive analysis of survival efficacies and microbial burden studies showed more consistent results with CAF0110µg /10µg vaccine formulation. Vaccines and antimicrobial drugs enhanced both survival efficacies and median survival time. The CAF0110µg /10µg vaccine induced a durable antibody and T cell immunity up to 270 days (9 months) post-vaccination. Finally, CAF0110µg /10µg vaccine- mediated protection was dependent on both antibodies and CD4 T cells. Thus, the study shows that the Als3p/Hyr1p (10ug/10µg) dual antigen vaccine formulated with CAF01 induced a robust protective immunity against Candida albicans and is cross-protective against multi-drug resistant C. auris and GNB (AB, KP and PA). REFERENCES Boucher HW, et al., Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clinical Infectious Diseases [Internet]. Oxford University Press (OUP); 2009;48(1):1–12. Available from: http://dx.doi.org/10.1086/595011 Spellberg B, et al., The Epidemic of Antibiotic-Resistant Infections: A Call to Action for the Medical Community from the Infectious Diseases Society of America. Clinical Infectious Diseases.2008 Jan 15;46(2):155–164. Attorney Docket No.022098-0583845 3. Higgins PG, et al,. Global spread of carbapenem-resistant Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy [Internet]. Oxford University Press (OUP); 2009;65(2):233– 238. 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Rudkin FM, et al., Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nat Commun.2018 Dec 11;9(1):5288. PMID: 30538246 95. Uppuluri P, et al., The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection. PLoS Pathog.2018 May;14(5):e1007056. PMID: 29746596 96. Saul A, Models of Phase 1 vaccine trials: optimization of trial design to minimize risks of multiple serious adverse events. Vaccine.2005 Apr;23(23):3068–3075. [00142] Throughout this application various publications have been referenced. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. Although the invention has been described with reference to the examples provided above, it should be understood that various modifications can be made without departing from the spirit of the invention. * * * [00143] The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure. [00144] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. [00145] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended Attorney Docket No.022098-0583845 as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. The use of such phrases, however, should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should typically be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” Attorney Docket No.022098-0583845 [00146] It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the technology. Therefore, it should be clearly understood that the forms of the technology are illustrative only and are not intended to limit the scope of the technology. [00147] All references cited herein are hereby incorporated by reference in their entirety. [00148] Embodiments will be described in more detail below. 1. A vaccine comprising a combination of an Als3p antigen, and Hyr1 antigen, and a pharmaceutically acceptable adjuvant. 2. The vaccine of 1, wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of aluminum compounds (e.g., alum, Alhydrogel®), oils, block polymers, immune stimulating complexes, vitamins and minerals (e.g., vitamin E, vitamin A, selenium, and vitamin B12), Quil A (saponins), bacterial and fungal cell wall components (e.g.lipopolysaccharides, lipoproteins, and glycoproteins), hormones, cytokines, co- stimulatory factors, and cationic adjuvants based on liposomes formed by N,N′-dimethyl- N,N′-dioctadecylammonium (DDA) with the synthetic mycobacterial immunomodulator α,α′- trehalose 6,6′-dibeheneate (TDB) inserted into the lipid bilayer, known as CAF01. 3. The vaccine of 2, wherein the adjuvant is CAF01. 4. The vaccine of 1, wherein the ratio of Als3p antigen to Hyr1 antigen ranges from about 10:1 to about 1:10. 5. A method of ameliorating a fungal infection or a fungal-bacterial mixed infection in a mammal comprising: administering to the mammal a therapeutically effective amount of the vaccine of 1. 6. The method of 5, wherein the mammal is a human. 7. The method of 5, wherein the adjuvant is CAF01 8. The method of 5, wherein the ratio of Als3p antigen to Hyr1 antigen ranges from about 10:1 to about 1:10. 9. The method of 5, further comprising administering to the mammal an antifungal drug. 10. The method of 5, wherein the fungal infection or the fungal-bacterial mixed infection is caused by Candida auris. Attorney Docket No.022098-0583845 11. The method of 5, wherein the fungal-bacterial mixed infection is caused in part by Gram negative bacteria. The method of any one of 1 to 11, wherein the fungal infection or the fungal-bacterial mixed infection is caused by a multidrug-resistant fungus or a multidrug-resistant bacterium.

Claims

Attorney Docket No.022098-0583845 What is claimed is: 1. A composition comprising: (a) an Als3p antigen comprising an immunogenic fragment of SEQ ID NO: 5; (b) an Hyr1 antigen comprising an immunogenic fragment of SEQ ID NO: 1; and (c) a pharmaceutically acceptable adjuvant. 2. The composition as claimed in claim 1, wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of aluminum compounds (e.g., alum, Alhydrogel®), oils, block polymers, immune stimulating complexes, vitamins and minerals (e.g., vitamin E, vitamin A, selenium, and vitamin B12), Quil A (saponins), bacterial and fungal cell wall components (e.g.lipopolysaccharides, lipoproteins, and glycoproteins), hormones, cytokines, co-stimulatory factors, and a cationic adjuvant based on liposomes formed by N,N′-dimethyl-N,N′-dioctadecylammonium (DDA) with the synthetic mycobacterial immunomodulator α,α′-trehalose 6,6′-dibeheneate (TDB) inserted into the lipid bilayer (CAF01). 3. The composition as claimed in claim 2, wherein the adjuvant is CAF01. 4. The composition as claimed in claim 1, wherein the Hyr1 antigen is selected from an SEQ ID NO: 4, or an antigen having at least 80% sequence identity to SEQ ID NO: 4. 5. The composition as claimed in claim 1, wherein the Als3p antigen is selected from SEQ ID NO: 6, or an antigen having at least 80% sequence identity to SEQ ID NO: 6. 6. The composition as claimed in claim 1, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen ranges from about 10:1 to about 1:10. 7. The composition as claimed in claim 6, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen ranges from about 3:1 to about 1:1. 8. The composition as claimed in claim 7, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen is about 1:1. Attorney Docket No.022098-0583845 9. A composition comprising: (a) an Als3p antigen comprising an SEQ ID NO: 5 or an immunogenic fragment thereof; (b) an Hyr1 antigen comprising SEQ ID No:1 or an immunogenic fragment thereof; and (c) a cationic adjuvant based on liposomes formed by N,N′-dimethyl-N,N′-dioctadecylammonium (DDA) with the synthetic mycobacterial immunomodulator α,α′-trehalose 6,6′-dibeheneate (TDB) inserted into the lipid bilayer (CAF01). 10. The composition as claimed in claim 9, wherein the Hyr1 antigen is selected from an SEQ ID NO: 4, or an antigen having at least 80% sequence identity to SEQ ID NO: 4. 11. The composition as claimed in claim 9, wherein the Als3p antigen is selected from SEQ ID NO: 6, or an antigen having at least 80% sequence identity to SEQ ID NO: 6. 12. The composition as claimed in claim 9, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen ranges from about 10:1 to about 1:10. 13. The composition as claimed in claim 9, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen ranges from about 3:1 to about 1:1. 14. The composition as claimed in claim 13, wherein the weight ratio of the Als3p antigen to the Hyr1 antigen is about 1:1. 15. A method of treating and/or preventing a fungal infection, a bacterial infection, or a fungal-bacterial mixed infection in a mammal comprising administering to the mammal a therapeutically effective amount of the composition of 1. 16. The method as claimed in claim 15, wherein the mammal is a human. 17. The method as claimed in claim 15, wherein the adjuvant is CAF01. 18. The method as claimed in claim 15, wherein the Hyr1 antigen is selected from SEQ ID NO: 4, or an antigen having at least 80% sequence identity to SEQ ID NO: 4. Attorney Docket No.022098-0583845 19. The method as claimed in claim 15, wherein the Als3p antigen is selected from SEQ ID NO: 6, or an antigen having at least 80% sequence identity to SEQ ID NO: 6. 20. The method as claimed in claim 15, wherein the weight ratio of Als3p antigen to Hyr1 antigen ranges from about 10:1 to about 1:10. 21. The method as claimed in claim 20, wherein the weight ratio of Als3p antigen to Hyr1 antigen is about 1:1. 22. The method as claimed in claim 15, further comprising administering to the mammal an antifungal drug. 23. The method as claimed in claim 15, wherein the fungal infection or the fungal- bacterial mixed infection is caused by Candida auris. 24. The method as claimed in claim 15, wherein the fungal-bacterial mixed infection is caused in part by Gram negative bacteria. 25. The method as claimed in claim 15, wherein the fungal infection, bacterial infection, or the fungal-bacterial mixed infection is caused by a multidrug-resistant fungus or a multidrug-resistant bacterium. 26. The method as claimed in claim 15, further comprising administering to the mammal an antimicrobial drug. 27. A method of treating and/or preventing a fungal infection, a bacterial infection, or a fungal-bacterial mixed infection in a mammal comprising administering to the mammal a therapeutically effective amount of the composition of 9.