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WO2025155702A1 - Hydrogels à base de cellulose utilisés en tant qu'adjuvants de vaccin - Google Patents

Hydrogels à base de cellulose utilisés en tant qu'adjuvants de vaccin

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Publication number
WO2025155702A1
WO2025155702A1 PCT/US2025/011844 US2025011844W WO2025155702A1 WO 2025155702 A1 WO2025155702 A1 WO 2025155702A1 US 2025011844 W US2025011844 W US 2025011844W WO 2025155702 A1 WO2025155702 A1 WO 2025155702A1
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WIPO (PCT)
Prior art keywords
hydrogel
cnf
tempo
tocnf
hydrogels
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Pending
Application number
PCT/US2025/011844
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English (en)
Inventor
Deborah BOUCHARD
Michael Mason
Sarah Turner
Blake TURNER
Kora KUKK
Jacob HOLBROOK
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University of Maine System
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University of Maine System
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Publication of WO2025155702A1 publication Critical patent/WO2025155702A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
    • C08B15/02—Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
    • C08B15/04—Carboxycellulose, e.g. prepared by oxidation with nitrogen dioxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
    • C08B15/02—Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/02—Cellulose; Modified cellulose
    • C08L1/04—Oxycellulose; Hydrocellulose, e.g. microcrystalline cellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/517—Plant cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552—Veterinary vaccine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55583—Polysaccharides

Definitions

  • Antibiotics have commonly been used for disease mitigation in finfish aquaculture, but have multiple drawbacks including resistance and leaching. Aquaculture loss due to disease is substantial. Solutions other than antibiotics have challenges. For example, vaccines using oil- based adjuvants can cause internal adhesions in the salmon peritoneal cavity. Salmon in particular may need to be vaccinated multiple times due to environmental factors and the condition of the fish. [0004] Disease outbreaks are a major impediment to aquaculture production and are forecast to continue as the industry grows and the climate warms. Vaccines are integral for disease management in aquaculture but they can be expensive, vary in effectiveness, and come with adjuvant-induced adverse effects causing fish welfare issues and negative economic impacts.
  • the vaccine composition further comprises one or more additional adjuvants, stabilizers, preservatives, surfactants, buffering agents, or culturing substances.
  • a vaccine composition comprising a salt crosslinked cellulose nanofibril (CNF) hydrogel; and an antigen or immunogen.
  • the vaccine composition is an injectable solution capable of passing through a 26-gauge needle.
  • the CNF hydrogel comprises TEMPO-oxidized CNF crosslinked with the salt.
  • the salt is NaCl or CaCl2.
  • the vaccine composition further comprises one or more additional adjuvants, stabilizers, preservatives, surfactants, buffering agents, or culturing substances.
  • the vaccine composition comprises bacterin.
  • a method of stimulating a foreign body response (FBR) in an Atlantic salmon comprising administering to an Atlantic salmon a vaccine composition comprising a citric acid TEMPO-oxidized CNF hydrogel and an immunogen.
  • a kit for making a vaccine comprising a first container housing a salt-crosslinked TEMPO-oxidized CNF hydrogel; and a second container housing an antigen or immunogen.
  • the second container houses bacterin.
  • a salt-crosslinked TEMPO-oxidized cellulose nanofibril (CNF) hydrogel as a vaccine adjuvant.
  • FIGS.12A-12B Hemorrhaging of ventral surface surrounding injection site as seen in Atlantic salmon mortalities injected with vaccine formulated with 2x EDC NHS amidated TOCNF (FIG. 12A) and 2x ODA DMF amidated TOCNF (FIG.12B).
  • FIG.13 Internal gross pathology observed in mortalities of Atlantic salmon vaccinated with 2x amidated TOCNF formulations including a.) pale liver, b.) external hemorrhaging surrounding the injection site, and c.) severe hemorrhaging near the formulation through the epidermal layer into the viscera with involvement of pyloric caeca.
  • FIG.15 Internal gross pathologies observed at the 300-degree day sampling time point in Atlantic salmon vaccinated with 2x amidated TOCNF formulations including a.) pale liver and b.) edema of the pyloric caeca.
  • FIG.16 FT-IR interferogram documenting changes in absorbance throughout the wash process during production of 1x amidated TOCNF of the entire absorbance spectrum for each sample (left) and a zoomed-in area of the absorbance spectrum between wavelengths of 3200 - 300 cm -1 (right).
  • FIGS.17A-17B Device to intraperitoneally implant TOCNF hydrogels into Atlantic salmon demonstrating PIT tagging implanter connected to 8-gauge stainless steel luer-lok needle with 3D printed plastic blunt stopper (black) attached to the plunger to deliver a TOCNF hydrogel (FIG.17A), and a close- up of the 8-gauge luer-lok needle pre-loaded with TOCNF hydrogel (FIG.17B).
  • FIGS.18A-18B Observed closed visible incision (FIG.18A) and lesion developed anteriorly from the closed incision site 600- degree days after implantation of TOCNF hydrogels with the improved implantation device (FIG.18B).
  • FIG.20 Photographic example of external pathologies observed, namely, a.) unhealed incision, b.) visible lesion, and c.) external proliferative mass during gross necropsy in Atlantic salmon at 600-degree days post-implantation with TOCNF hydrogel.
  • CNFs can be extracted from cellulose pulp through mechanical shearing or through a combination of both mechanical and chemical methods such as high-pressure homogenization, grinding, cryocrushing, and high intensity ultrasonic treatment.
  • Mechanical methods may involve grinding or homogenizing the cellulose material to break it down into nanoscale fibrils, while chemical methods use specific treatments to isolate the nanofibrils. The more shearing that occurs, the more cellulose fibers are cleaved transversely to produce finer sized fibers in the nano- to micron scale.
  • Chemical treatments used to obtain CNF may include acid hydrolysis, oxidative treatments, enzymatic hydrolysis, or alkaline treatments.
  • Cellulose nanofibrils can be used to form hydrogels through various methods such as, but not limited to, physical cross-linking, chemical cross-linking, or a combination of both. As depicted in FIG.1, CNF hydrogels have a closer fiber aggregation compared to CNF due to the addition of salts. [0054] When CNF is obtained by a TEMPO process, the CNF has distinctive characteristics compared to CNFs obtained through other methods.
  • the TEMPO process involves the use of a radical initiator (TEMPO) and NaClO to selectively oxidize the primary hydroxyl groups of cellulose.
  • TEMPO radical initiator
  • NaClO NaClO
  • TEMPO-oxidized CNF also referred to as TEMPO CNF
  • CNF hydrogels have been used in various veterinary and biomedical applications due to their bioinert nature.
  • Salt bridging enhances the mechanical properties of TEMPO including stability in aqueous solutions. Salts shield the negative charge of TEMPO fibers allowing for closer aggregation of fibers. Closer fiber aggregation and salt bridging results in improved gel strength.
  • CNFs obtained from non-TEMPO process may also, or alternatively, be used to form the salt-crosslinked CNF hydrogels described herein, and used as adjuvants in vaccine compositions.
  • CNF hydrogels can absorb and retain large amounts of water. This is advantageous for drug delivery as it can help in solubilizing and delivering hydrophilic drugs effectively. CNF hydrogels may be transparent, making them suitable for certain optical or medical applications.
  • CNF hydrogels are ideal for drug delivery because of their tunability and ability to encapsulate both water soluble and insoluble molecules for the sustained release of the desired drug. With this sustained release, the immune system can be triggered and create a desired immune response for a longer period of time compared to conventional drug delivery systems.
  • CNF hydrogels are also useful for drug delivery because of their biocompatibility and ability to mimic the extracellular matrix.
  • CNF hydrogels are biocompatible and can be well-tolerated by the body, which is important for adjuvant applications as it ensures that the adjuvant does not induce adverse reactions or toxicity.
  • CNF hydrogels may be able to alter their physical properties such as phase transition, swelling, or degree of crosslinking depending upon the stimulus.
  • CNF hydrogels can be responsive to both chemical and physical responses.
  • CNF hydrogels can provide sustained release of drugs over time.
  • the three-dimensional network structure of the hydrogel (FIG.1), formed by the cellulose nanofibrils, allows for controlled diffusion of drugs from the gel matrix.
  • the examples herein demonstrate the controlled diffusion of a dye from a CNF hydrogel (FIGS.3A-3B).
  • CNF hydrogels can encapsulate various types of drugs, including both hydrophilic and hydrophobic compounds. This versatility makes CNF hydrogels suitable for a wid range of pharmaceutical applications.
  • modified CNF such as TEMPO-oxidized CNF
  • TEMPO-oxidized CNF is easier for forming a hydrogel.
  • Suitable crosslinkers for forming a hydrogel with TEMPO-oxidized CNF include, but are not limited to, polyethyleneimine, heavy metals (such as Fe 3+ and Ca 2+ ), citric acid, dialdehydes, acetals, polycarboxylic acids, and epichlorohydrin/polyepichlorohydrin.
  • a salt-crosslinked TEMPO-oxidized CNF hydrogel may be prepared by mixing a salt with TEMPO- oxidized CNF to crosslink the TEMPO-oxidized CNF.
  • the salt may be, for example, NaCl or CaCl 2 .
  • salt-crosslinked the actual species accomplishing the crosslinking may be a cation from the salt, such as Na + or Ca 2+ .
  • the terms “salt-crosslinked” and “salt crosslinked” are used herein to encompass cation-crosslinked embodiments where the cation is provided from a salt.
  • the cation of a salt may crosslink carboxyl groups on different nanofibrils of the CNF, as illustrated in FIG.1 using Ca 2+ cations as an example.
  • other salts or cross linkers are possible and encompassed within the scope of the present disclosure.
  • the TEMPO-oxidized CNF is crosslinked with citric acid to form a CNF hydrogel.
  • salt-crosslinked TEMPO- oxidized hydrogels exhibit shear-thinning behavior and are injectable solutions capable of passing through a 26-gauge needle. Shear-thinning hydrogels have improved injectability, moldability, and self-healing characteristics. Shear thinning is attributed to a hydrogel’s ability to rearrange and realign its polymer chains and chemical network when under various stimuli.
  • salt- crosslinked TEMPO-oxidized CNF hydrogels are useful as vaccine adjuvants.
  • the formulation of a CNF- based hydrogel as an injectable solution should avoid eliciting the foreign body response in an animal injected with a vaccine composition that includes the CNF-based adjuvant.
  • concentrations of the salt used to crosslink the TEMPO-oxidized CNF should be kept within certain limits.
  • the salt may be used in a concentration of up to about 7.14 mM when the salt is CaCl2, or up to a concentration of about 114 mM when the salt is NaCl.
  • these concentrations of salt are significantly less than the concentrations of cation crosslinkers previously used to physically crosslink CNF.
  • CaCl2 may be used in concentrations of about 7.14 mM, 4.66 mM, or 1.8 mM.
  • NaCl may be used in concentrations of 114 mM, 69 mM, or 23 mM.
  • TEMPO-oxidized CNF concentration exceeds 3 wt%, then the resulting hydrogel may be difficult to push through a 26-gauge needle.
  • carboxylic acid groups present on TEMPO-oxidized CNF are easily conjugated through an amide bond. This amide bond occurs when an amine group (-NH 2 ) reacts with a carboxylic acid group (-CONH-), causing the amine group to bond to the carboxylic acid. This process of amide bonding onto the carboxylic acid is referred to as amidation. Through this process, the overall characteristics of the TEMPO CNFs are altered without compromising the overall solubility of the polymer.
  • Rheometry is the study of the flow and deformation of materials, particularly liquids and soft solids, under the influence of applied forces or stresses. Rheometry measures the rheological properties of materials to understand their flow characteristics and mechanical responses.
  • the salt-crosslinked TEMPO-oxidized CNF hydrogels with the above-described salt concentrations exhibit shear-thinning behavior (FIGS.2A-2B). This means that the viscosity decreases with an increase in shear rate.
  • the salt-crosslinked TEMPO-oxidized CNF hydrogels experience higher rates of shear or deformation, they become less resistant to flow.
  • Certain biological fluids, such as synovial fluid in joints, mucus, and blood are also shear-thinning.
  • the salt-crosslinked TEMPO-oxidized CNF hydrogels exhibit shear-thinning behavior which is advantageous in a vaccine composition to facilitate ease of administration of the vaccine composition.
  • the adjuvant compositions and vaccine compositions described herein are injectable solutions that can pass through a 26-gauge needle. This is highly advantageous because most aquaculture vaccination methods utilize a 26-gauge needle and syringe to administer the vaccination into aquatic animals.
  • CNF hydrogels can be combined with other materials or polymers to create hybrid systems with enhanced properties, such as improved drug loading capacity or controlled release profiles.
  • a CNF hydrogel may be loaded with bacterin to vaccinate an animal.
  • Vaccine compositions may include a CNF hydrogel, an antigen or immunogen, and optionally one or more additional adjuvants, stabilizers, preservatives, surfactants, buffering agents, or culturing substances.
  • the vaccine compositions may include an antigen or immunogen bound to CNF hydrogel or otherwise incorporated in the CNF hydrogel.
  • the inherent mechanical strength of CNF contributes to the overall stability and integrity of the vaccine compositions during handling and administration.
  • CNF is also particularly suitable for vaccine compositions because of its biocompatibility.
  • the adjuvant and vaccine compositions described herein may also be made available via a kit containing one or more key components.
  • Example I Salt crosslinked TEMPO-oxidized CNF hydrogels
  • This example demonstrates the efficacy of NaCl and CaCl2 as crosslinkers to form CNF hydrogels, and the usefulness of the resulting CNF hydrogels as vaccine adjuvants which do not cause a foreign body response in Atlantic salmon.
  • CNF hydrogels were prepared according to the following procedures.
  • Preparation of salt-crosslinked TEMPO CNF [0071] Solutions of salt were prepared. 0.9 M for CaCl2 was prepared by dissolving 5 g CaCl2 in 50 ml of water.
  • FIGS.3A-3B show the diffusion of a dye out of the crosslinked hydrogels.
  • NaCl hydrogels had similar diffusion characteristics across all concentrations, and CaCl2 hydrogels exhibited similar diffusion characteristics.
  • Salmon safety trial [0081] A safety trial was conducted using the salt crosslinked TEMPO-oxidized CNF hydrogels in Atlantic salmon. Salmon smolt were administered a fluorescent tag or a vaccination with CNF hydrogel, as shown in the photographs in FIGS.4A-4B. The 300-day results are shown in FIG.4C. The 300-day results showed no mortalities recorded across all formulations. Most of the hydrogels were recovered from the peritoneal cavity of the salmon.
  • salt crosslinked TEMPO-oxidized CNF hydrogel vaccine compositions did not cause a foreign body response in the salmon.
  • the salt crosslinked TEMPO CNF hydrogels were more stable in aqueous solutions than other hydrogels, had greater gel stiffness than other hydrogels, and could impact diffusion rates from the hydrogel matrix.
  • Salt crosslinked TEMPO hydrogels were found to be shear-thinning using cone and plate rheometry (40 mm 2° cone), were easily injectable through a 26-gauge needle, and did not cause a foreign body response in Atlantic salmon.
  • Example II Toxicity and immunogenicity of intraperitoneally injected shear-thinning TEMPO-oxidized cellulose nanofiber hydrogels produced and characterized for antigen delivery in an Atlantic salmon (Salmo salar L.) vaccine
  • This example describes the preparation of an injectable shear-thinning vaccine using cellulose nanomaterials (CNM) as a crosslinked adjuvant matrix; the in vitro characterization of the mechanical, structural, and chemical properties of the CNM adjuvanted vaccine formulations using rheology, scanning electron microscopy, and Fourier-Transform Infrared spectroscopy; an in vivo examination of toxicity in Atlantic salmon compared to a commercial adjuvanted Montanide control; and the quantification of immunogenicity using gene expression and serological antigen specific antibody response by indirect ELISA assay compared to commercial adjuvanted Montanide control.
  • CCM cellulose nanomaterials
  • the spectrums were recorded on a diamond plate with a resolution of 4 cm -1 with 128 scans.
  • the Attenuated Total Reflection (ATR) auto-correction parameter was enabled for higher precision.
  • the wavelength of the spectrum was set from 4000 to 400 cm -1 .
  • Prior to sample acquisition, the background was set to the same parameters as sample acquisition.
  • Liquid and amidated TOCNF samples 200 ⁇ L were loaded onto the diamond plate and covered to limit evaporation during sampling. Solid samples fully covered the diamond plate in powdered form before the ATR compression arm was engaged.
  • the absorbance spectrums were separated for comparison by graphing manually with offset Y-axis values.
  • the reference gene ⁇ -actin was used to normalize the expression levels of the target genes. All primers of the target and reference genes were synthesized by the Integrated DNA Technologies (IDT, Morrisville, NC, USA). The amplification efficiencies of the target and reference genes were quantified according to the specific gene standard curves generated from 10-fold serial dilutions. After verifying that the primers were amplified with 100% efficiency, the relative expression results were analyzed using the 2 ⁇ Ct method. [00125] Serological antigen specific antibody response by indirect ELISA [00126] Tetrameric immunoglobulin M (IgM) is the prominent immunoglobulin found in salmonid serum with a primary function being systemic immunity.
  • IgM Tetrameric immunoglobulin M
  • Table 8 Results of the Mantel-Haenszel hazard ratios of vaccinating Atlantic salmon with the sham negative control groups and amidated TOCNF groups compared to the commercial oil-adjuvanted positive control group at 600 degree-days post-injection showing Gehan-Breslow-Wilcoxon analysis Formulation % % Cumulative M-H Odds Ratio (95% Cumulative Survival CI) ⁇ 2 (df), p-value Incidence (No. (No. Morts/ Censored/ No. No.
  • External and Internal Gross Examination [00203] Gross necropsy was performed on all fish to assess adverse reactions to uptake of and dispersion of TOCNF hydrogels. Therefore, complete external and internal gross examinations were performed at 300 and 600-degree days post-implantation. External examination evaluated incision healing and presence of external lesions including protruding proliferative tissue. Internal visceral and peritoneal adhesions, melanization, fibrosis, granuloma formation, and hydrogel residue were evaluated and scored based on a modified Speilberg scale (Table 14).
  • Histology tissues were collected and analyzed.
  • Histopathology [00205] At the conclusion of the in vivo biocompatibility study (600-degree days post-implantation), tissue samples were collected from 4 fish per treatment group per duplicate tank for a total of 40 samples and fixed into 35 mLs of 10% neutral buffered formalin (Fisher Scientific). Tissues included approximately 1 cm 2 of body wall at the implantation site, the pyloric caeca, liver, a digestive tract, and spleen. Tissues were submitted to the New Hampshire Veterinary Diagnostic Laboratory (NHVDL) for histopathologic processing and evaluation.
  • NHS New Hampshire Veterinary Diagnostic Laboratory
  • DPBS + the Vibrio anguillarum bacterin was injected into the incision using a 1 mL syringe with 28-gauge needle and served as a negative control in five fish per duplicate tank (10 fish total) to compare acute gross pathology. Following implantation, fish were immediately returned to the respective tanks for recovery. Two fish per treatment per tank (4 fish per treatment) at each timepoint of 0, 12-, 24-, 48-, and 72-hours post-implantation (8 fish per timepoint) were sampled by euthanizing fish with a lethal dose of MS-222 supplemented with sodium bicarbonate. To verify all fish had a healthy body condition (K ⁇ 1.0), sampling was performed for collecting biometric data of weights (g) and fork length (cm).
  • Fulton’s condition factor (K) was calculated using 100WL -3 where W is body weight (g) and L is fork length (cm), so that differences in condition of the fish vaccinated with the different formulations could be compared.
  • Prevalence of adverse reactions (%) ranging from mild to severe as observed using the modified Spielberg scoring growth data were analyzed at each time point by treatment.

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  • Polymers & Plastics (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Materials Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
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Abstract

L'invention concerne des compositions d'adjuvant et des compositions de vaccin utilisant les compositions d'adjuvant. Les compositions d'adjuvant comprennent un hydrogel de nanofibrilles de cellulose (CNF) à oxydation TEMPO et à réticulation par un sel, et les compositions de vaccin comprennent en outre un antigène ou un immunogène.
PCT/US2025/011844 2024-01-19 2025-01-16 Hydrogels à base de cellulose utilisés en tant qu'adjuvants de vaccin Pending WO2025155702A1 (fr)

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US63/622,892 2024-01-19

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8105682B2 (en) * 2006-09-01 2012-01-31 The Regents Of The University Of California Thermoplastic polymer microfibers, nanofibers and composites
US20210077403A1 (en) * 2019-09-13 2021-03-18 Upm-Kymmene Corporation Method for preparing pharmaceutical composition and pharmaceutical composition
US20220195148A1 (en) * 2018-03-29 2022-06-23 The Regents Of The University Of California Nanocellulose aerogels and foams
US20230301906A1 (en) * 2020-07-31 2023-09-28 Ocean Tunicell As Biocompatible, injectable and in situ gelling hydrogels and preparation and applications of biocompatible, injectable and in situ gelling hydrogels based on cellulose nanofibrils for tissue and organ repair

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8105682B2 (en) * 2006-09-01 2012-01-31 The Regents Of The University Of California Thermoplastic polymer microfibers, nanofibers and composites
US20220195148A1 (en) * 2018-03-29 2022-06-23 The Regents Of The University Of California Nanocellulose aerogels and foams
US20210077403A1 (en) * 2019-09-13 2021-03-18 Upm-Kymmene Corporation Method for preparing pharmaceutical composition and pharmaceutical composition
US20230301906A1 (en) * 2020-07-31 2023-09-28 Ocean Tunicell As Biocompatible, injectable and in situ gelling hydrogels and preparation and applications of biocompatible, injectable and in situ gelling hydrogels based on cellulose nanofibrils for tissue and organ repair

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