WO2025055944A1

WO2025055944A1 - Treatment and prevention of hepatitis b using covid-19 vaccine

Info

Publication number: WO2025055944A1
Application number: PCT/CN2024/118280
Authority: WO
Inventors: John Qi ZHANG
Original assignee: Individual
Current assignee: Individual
Priority date: 2023-09-11
Filing date: 2024-09-11
Publication date: 2025-03-20
Anticipated expiration: 2026-03-11

Abstract

Provided are treatment and prevention of hepatitis B. In particular, provided is a method for treating or preventing hepatitis B in a subject, the method comprises: administering effective amount of COVID-19 vaccine to the subject. Further provided is use of COVID-19 vaccine in manufacturing a drug for treating or preventing hepatitis B.

Description

TREATMENT AND PREVENTION OF HEPATITIS B USING COVID-19 VACCINE

TECHNICAL FIELD

The present disclosure relates to treatment and prevention of hepatitis B. In particular, the present disclosure relates to a method for treating or preventing hepatitis B in a subject, the method comprises: administering effective amount of COVID-19 vaccine to the subject. The present disclosure further relates to use of COVID-19 vaccine in manufacturing a drug for treating or preventing hepatitis B.

BACKGROUND

The World Health Organization (WHO) estimates that 296 million people were living with hepatitis B infection in 2019, with 1.5 million new infections each year. Hepatitis B is a viral infection that affects the liver and can cause chronic liver disease, cirrhosis, liver cancer, and death.

Hepatitis B vaccines are designed to prevent hepatitis B infection by inducing protective immunity against the hepatitis B surface antigen (HBsAg) , which is a protein on the surface of the virus. There are two types of hepatitis B vaccines: plasma-derived and recombinant. Plasma-derived vaccines are made from purified HBsAg obtained from the blood of people who are infected with hepatitis B. Recombinant vaccines are made from genetically engineered yeast or mammalian cells that produce HBsAg. The introduction of plasma hepatitis B vaccine in 1981, especially the universal use of the recombinant hepatitis B vaccine in 1986 to the newborn have greatly reduce the infection of hepatitis B worldwide. However, it remains unclear what proportion of individuals who complete all 3 shot schedules of hepatitis B vaccine achieve full protection, as was found in an earlier study where 22.9%of vaccinated children had undetected antibody levels.

There is no specific eradication treatment for hepatitis B. Current available treatment for hepatitis B is oral antiviral agents (e.g., tenofovir or entecavir) , aiming to slow the progression of cirrhosis, reduce incidence of liver cancer and improve long term survival. Most patients who start hepatitis B treatment must continue it for life.

Therefore, treatment and prevention of hepatitis B have been an ever-ongoing topic for scientists and clinicians.

SUMMARY

The present disclosure solves the problem regarding treatment and prevention of hepatitis B. Surprisingly, the inventor of the present disclosure found that, (1) COVID-19 vaccine induced production of enough amount of HBsAb to eradicate hepatitis B viruses, hence, to achieve total cure of hepatitis B, and the HBsAb titers sustained long enough to provide hepatitis B patients lifetime immunity against Hepatitis B, and (2) COVID-19 vaccine induced exponential increasement in HbsAb titer in healthy persons and can be used as an effective way for preventing Hepatitis B to protect the general public.

One aspect of the present disclosure relates to a method for treating or preventing hepatitis B in a subject, the method comprises:

administering effective amount of COVID-19 vaccine to the subject.

Another aspect of the present disclosure relates to use of COVID-19 vaccine in manufacturing a drug for treating or preventing hepatitis B.

DETAILED DESCRIPTION

The present disclosure is explained in greater detail below. This description is not intended to be a detailed catalog of all the different ways in which the present disclosure may be implemented, or all the features that may be added to the present disclosure. For example, features illustrated with respect to one embodiment may be incorporated into other embodiments, and features illustrated with respect to a particular embodiment may be deleted from that embodiment. In addition, numerous variations and additions to the various embodiments suggested herein will be apparent to those skilled in the art in light of the instant disclosure which do not depart from the present disclosure. Hence, the following description is intended to illustrate some particular embodiments of the present disclosure, and not to exhaustively specify all permutations, combinations and variations thereof.

Unless the context indicates otherwise, it is specifically intended that the various features of the present disclosure described herein can be used in any combination. Moreover, the present disclosure also contemplates that in some embodiments of the present disclosure, any feature or combination of features set forth herein can be excluded or omitted. To illustrate, if the description states that a complex comprises components A, B and C, it is specifically intended that any of A, B or C, or a combination thereof, can be omitted and disclaimed singularly or in any combination.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains. Although any methods and materials similar or equivalent to those described herein may be used in the practice for testing of the present disclosure, the preferred materials and methods are described herein. In describing and claiming the present disclosure, the following terminology will be used.

It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

The singular forms “a, ” “an, ” and “the” include plural referents unless the context clearly dictates otherwise.

As used in the description and in the claims, the open-ended transitional phrases “comprise (s) ” , “comprising” , “include (s) ” , “including” , “have” , “has” , “having” , “contain (s) ” , “containing” and variants thereof require the presence of the named ingredients/steps and permit the presence of other ingredients/steps. These phrases should also be construed as disclosing the closed-ended phrases “consist of” or “consist essentially of” that permit only the named ingredients/steps and unavoidable impurities and exclude other ingredients/steps.

Numerical values in the description and claims of this application should be understood to include numerical values which are the same when reduced to the same number of significant figures and numerical values which differ from the stated value by less than the experimental error of conventional measurement technique of the type described in the present application to determine the value.

The advent of COVID-19 pandemic from November 2019, and the following successful sequencing of the causative virus SARS-CoV-2 in January 2020, led to the rapid development and the wide EUA of mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna. The widely vaccination with COVID-19 vaccine in the past three years in hepatitis B patients and healthy persons have enable the inventor of the present disclosure not only with surprised discovery that the COVID-19 vaccine therapeutically achieved total clearance of hepatitis B virus from large numbers of hepatitis B patients and sustained high HBsAb titer to provide lifetime immunity against hepatitis B virus, but with findings that the COVID-19 vaccine can replace current recombinant hepatitis B vaccine for protection of hepatitis B infection, or at least that the COVID-19 vaccine can be used as booster vaccine for those nonresponders from routine recombinant hepatitis B vaccination, for those whose HBsAb have declined to nonprotected levels, for those high risk patients e.g., health care workers, drug abusers, HIV patients or other immunocompromised patients who may otherwise developed suboptimal HBsAb.

In a first aspect of the present disclosure, there is provided a method for treating or preventing hepatitis B in a subject, the method comprises:

administering effective amount of COVID-19 vaccine to the subject.

The term “treating” , “treat” , or “treatment” in connection with a disease or disorder as used herein embraces cure and palliative treatment, including reversing, relieving, alleviating, eliminating, or slowing the progression of the disease or disorder, or one or more symptoms of the disease or disorder, or any tissue damage associated with one or more symptoms of the disease or disorder.

The term “prevention” , “prevent” or “preventing” in connection with a disease or disorder as used herein refers to delaying or forestalling the onset or development of the disease or disorder a period of time from minutes to indefinitely. The term also includes prevention of the appearance of symptoms of the disease or disorder. The term further includes reducing the risk of developing the disease or disorder.

The term “hepatitis B” as used herein embraces hepatitis B itself as well as any disease, disorder, condition, or symptom resulting from hepatitis B virus infection, including but not limited to pain, edema, asthenia, emaciation, abdominal distension, dizziness, chronic liver disease, cirrhosis, liver cancer, and death.

The terms “effective amount” as used herein refers to an amount of a vaccine, which when administered to a subject in need thereof, is sufficient to effect treatment or prevention for hepatitis B. Such an amount would be sufficient to elicit the biological or medical response of a tissue system, or subject that is sought by a researcher or clinician. The amount of a vaccine which constitutes an effective amount will vary depending on such factors as the vaccine and its biological activity, the administration interval, the duration, the type of disease-state or disorder being treated and its severity, drugs used in combination with or coincidentally with the vaccine, and the age, body weight, general health, sex and diet of the subject. Such an effective amount can be determined routinely by one of ordinary skills in the art having regard to their own knowledge, the state of the art, and this disclosure.

The term “subject” as used herein embraces both hepatitis B patients and healthy persons. A healthy person refers to an individual without hepatitis B infection, as used herein.

In some embodiments, the COVID-19 vaccine comprises mRNA COVID-19 vaccine.

In some embodiments, the COVID-19 vaccine comprises any one, any two, any three or all of BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.

In some embodiments, the COVID-19 vaccine comprises at least 10 μg, at least 20 μg, at least 30 μg, at least 40 μg, at least 50 μg, at least 60 μg, at least 70 μg, at least 80 μg, at least 90 μg, or at least 100 μg BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna or mRNA-1273.211 from Moderna.

In some embodiments, one shot, two shots, three shots, four shots or more shots of COVID-19 vaccine is/are administrated to the subject.

In some embodiments, one shot of COVID-19 vaccine is administrated to the subject.

In some embodiments, more than one shot of COVID-19 vaccine is administrated to the subject, and the shots are the same or different COVID-19 vaccine.

In some embodiments, more than one shot of COVID-19 vaccine is administrated to the subject, and the shots independently from one another comprises any one, any two, any three or all of BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.

In some embodiments, more than one shot of COVID-19 vaccine is administrated to the subject, and the shots independently from one another comprises at least 10 μg, at least 20 μg, at least 30 μg, at least 40 μg, at least 50 μg, at least 60 μg, at least 70 μg, at least 80 μg, at least 90 μg, or at least 100 μg BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna or mRNA-1273.211 from Moderna.

The term “independently from one another” as used herein refers to referenced groups being the same, different, or a mixture thereof, unless the context clearly indicates otherwise. Thus, under this definition, the phrase “X1, X2, and X3 are independently selected from Y1, Y2, Y3 and Y4”would include the scenario where, for example, X1, X2, and X3 are all the same, where X1, X2, and X3 are all different, where X1 and X2 are the same but X3 is different, and other analogous permutations.

In some embodiments, two shots of COVID-19 vaccine are administrated to the subject, and the two shots independently from one another are selected from BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.

In some embodiments, two shots of COVID-19 vaccine are administrated to the subject, and the two shots are both BNT162b2 from Pfizer-BioNTech. In some embodiments, two shots of COVID-19 vaccine are administrated to the subject, and the two shots are both mRNA-1273.211 from Moderna. In some embodiments, two shots of COVID-19 vaccine are administrated to the subject, and the two shots are BNT162b2 from Pfizer-BioNTech and mRNA-1273.211 from Moderna, respectively, wherein BNT162b2 from Pfizer-BioNTech may be the first shot or the second shot.

In some embodiments, three shots of COVID-19 vaccine are administrated to the subject, and the three shots independently from one another are selected from BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.

In some embodiments, three shots of COVID-19 vaccine are administrated to the subject, and the three shots are all BNT162b2 from Pfizer-BioNTech. In some embodiments, three shots of COVID-19 vaccine are administrated to the subject, and the three shots are all mRNA-1273.211 from Moderna. In some embodiments, three shots of COVID-19 vaccine are administrated to the subject, and the three shots comprise two shots of BNT162b2 from Pfizer-BioNTech and one shot of mRNA-1273.211 from Moderna, wherein mRNA-1273.211 from Moderna may be the first, second or third shot; or one shot of BNT162b2 from Pfizer-BioNTech and two shots of mRNA-1273.211 from Moderna, wherein BNT162b2 from Pfizer-BioNTech may be the first, second or third shot.

In some embodiments, four shots of COVID-19 vaccine are administrated to the subject, and the four shots independently from one another are selected from BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.

In some embodiments, four shots of COVID-19 vaccine are administrated to the subject, and the four shots are all BNT162b2 from Pfizer-BioNTech. In some embodiments, four shots of COVID-19 vaccine are administrated to the subject, and the four shots are all mRNA-1273.211 from Moderna. In some embodiments, four shots of COVID-19 vaccine are administrated to the subject, and the four shots comprise three shots of BNT162b2 from Pfizer-BioNTech and one shot of mRNA-1273.211 from Moderna, wherein mRNA-1273.211 from Moderna may be the first, second, third or fourth shot; or one shot of BNT162b2 from Pfizer-BioNTech and three shots of mRNA-1273.211 from Moderna, wherein BNT162b2 from Pfizer-BioNTech may be the first, second, third or fourth shot; or two shots of BNT162b2 from Pfizer-BioNTech and two shots of mRNA-1273.211 from Moderna, wherein BNT162b2 from Pfizer-BioNTech may be the first shot and the second shot, or the first shot and the third shot, or the first shot and the fourth shot, or the second shot and the third shot, or the second shot and the fourth shot, or the third shot and the fourth shot.

In some embodiments, the interval between two adjacent shots, independently from one another, is selected from 1 week or longer, 2 weeks or longer, 3 weeks or longer, 1 month or longer, 2 months or longer, 3 months or longer, 4 months or longer, 5 months or longer, 6 months or longer, 7 months or longer, 8 months or longer, 9 months or longer, 10 months or longer, 11 months or longer, 1 year or longer, 1.5 years or longer, 2 years or longer, and 3 years or longer.

In the case of two shots of COVID-19 vaccine being administrated to the subject, “two adjacent shots” refers to the first shot and the second shot. In this situation, the interval between the first shot and the second shot is selected from 1 week or longer, 2 weeks or longer, 3 weeks or longer, 1 month or longer, 2 months or longer, 3 months or longer, 4 months or longer, 5 months or longer, 6 months or longer, 7 months or longer, 8 months or longer, 9 months or longer, 10 months or longer, 11 months or longer, 1 year or longer, 1.5 years or longer, 2 years or longer, and 3 years or longer.

In the case of three shots of COVID-19 vaccine being administrated to the subject, “two adjacent shots” comprises the first shot and the second shot, as well as the second shot and the third shot. In this situation, the interval between the first shot and the second shot and the interval between the second shot and the third shot, independently from one another, are selected from 1 week or longer, 2 weeks or longer, 3 weeks or longer, 1 month or longer, 2 months or longer, 3 months or longer, 4 months or longer, 5 months or longer, 6 months or longer, 7 months or longer, 8 months or longer, 9 months or longer, 10 months or longer, 11 months or longer, 1 year or longer, 1.5 years or longer, 2 years or longer, and 3 years or longer.

In the case of four shots of COVID-19 vaccine being administrated to the subject, “two adjacent shots” comprises the first shot and the second shot, the second shot and the third shot, as well as the third shot and the fourth shot. In this situation, the interval between the first shot and the second shot, the interval between the second shot and the third shot, and the interval between the third shot and the fourth shot, independently from one another, are selected from 1 week or longer, 2 weeks or longer, 3 weeks or longer, 1 month or longer, 2 months or longer, 3 months or longer, 4 months or longer, 5 months or longer, 6 months or longer, 7 months or longer, 8 months or longer, 9 months or longer, 10 months or longer, 11 months or longer, 1 year or longer, 1.5 years or longer, 2 years or longer, and 3 years or longer.

In some embodiments, the method further comprises: determining hepatitis B surface antibody (HBsAb) titer of the subject, and

administering another shot of COVID-19 vaccine, if the HBsAb titer is determined to be lower than 10 mIU/mL.

In some embodiments, the method further comprises: administering one or more medicines for treatment or prevention of hepatitis B, prior to, simultaneously with, and/or following the administration of COVID-19 vaccine.

As used herein, the expression “A and/or B” includes three cases: (1) A, (2) B, and (3) A and B; and the expression “A, B and/or C” includes seven cases: (1) A, (2) B, (3) C, (4) A and B, (5) A and C, (6) B and C, and (7) A and B and C; and so on.

In some embodiments, administering a first medicine for treatment or prevention of hepatitis B prior to the administration of COVID-19 vaccine, administering a second medicine for treatment or prevention of hepatitis B simultaneously with the administration of COVID-19 vaccine, and/or administering a third medicine for treatment or prevention of hepatitis B following the administration of COVID-19 vaccine.

The first medicine, the second medicine and the third medicine may be the same or different. For example, the first medicine, the second medicine and the third medicine may be all the same. For example, the first medicine, the second medicine and the third medicine may be all different. For example, the first medicine and the second medicine may be the same and the third medicine may be different. For example, the first medicine and the third medicine may be the same and the second medicine may be different. For example, the second medicine and the third medicine may be the same and the first medicine may be different.

In some embodiments, the first medicine may be a single medicine or a combination of two or more medicines. In some embodiments, the second medicine may be a single medicine or a combination of two or more medicines. In some embodiments, the third medicine may be a single medicine or a combination of two or more medicines.

In some embodiments, the one or more medicines include but are not limited to antiviral nucleotide medicine (e.g. entecavir, tenofovir, viread) , interferon medicine (e.g. peginterferon alfa-2a, peginterferon alfa-2b) , liver protection medicine (e.g. compound glycyrrhizin, bifendate, silymarin) , and the like.

In some embodiments, at least one medicine comprises antiviral nucleotide medicine.

In some embodiments, at least one medicine comprises entecavir, tenofovir, lamivudine, telbivudine, adefovir dipivoxil, tenofovir alafenamide and/or viread.

In some embodiments, the first medicine may comprise any one, any two, any three or more of entecavir, tenofovir, lamivudine, telbivudine, adefovir dipivoxil, tenofovir alafenamide and viread. In some embodiments, the second medicine may comprise any one, any two, any three or more of entecavir, tenofovir, lamivudine, telbivudine, adefovir dipivoxil, tenofovir alafenamide and viread. In some embodiments, the third medicine may comprise any one, any two, any three or more of entecavir, tenofovir, lamivudine, telbivudine, adefovir dipivoxil, tenofovir alafenamide and viread.

In a second aspect of the present disclosure, there is provided use of COVID-19 vaccine in manufacturing a drug for treating or preventing hepatitis B.

In some embodiments, the COVID-19 vaccine comprises mRNA COVID-19 vaccine.

In some embodiments, the drug is a hepatitis B vaccine.

In some embodiments, the drug is an injection, inhalant, oral formulation, topical formulation or implant.

The technical solution of the present disclosure will be more clearly and explicitly described by way of illustration in combination with examples. It should be understood that these examples are only for illustrative purposes and not intended to limit the protection scope of the present disclosure. The protection scope of the present disclosure is only defined by the appended claims.

EXAMPLES

Throughout the study period, no subject received any plasma-derived or recombinant hepatitis B vaccine in the market or any other new treatment or unknown vaccination.

Example 1

Subject 1 is an 83-year-old hepatitis B patient. The HbsAg of Subject 1 was measured to be positive abnormal on 10/22/2011 and 10/15/2011, and the HbsAb of Subject 1 was measured to be negative on 10/9/2012, 10/22/2011 and 10/15/2011. Subject 1 received BNT162b1 from Pfizer-BioNTech on 2/6/2021, 2/27/2021, 11/8/2021, 4/27/2022, respectively. The HbsAb titer of Subject 1 was measured to be 52.46 mIU/ml on 12/15/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 181 mIU/ml on 6/15/2023. Also, the HbsAg of Subject 1 was measured to be negative on 6/15/2023.

Example 2

Subject 2 is a 52-year-old hepatitis B patient. Subject 2 received BNT162b1 from Pfizer-BioNTech on 4/20/2021, 5/11/2021, 12/10/2021, respectively. The HbsAb titer of Subject 2 was measured to be 138 mIU/ml on 2/9/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 91.6 mIU/ml on 7/19/2023. Also, the HbsAg of Subject 2 was measured to be negative on 7/19/2023.

Example 3

Subject 3 is a 61-year-old hepatitis B patient. The HbsAg of Subject 3 was measured to be positive abnormal on 5/21/2014, and the HbsAb of Subject 3 was measured to be negative on 7/29/2015. Subject 3 received BNT162b1 from Pfizer-BioNTech on 4/13/2021, 5/4/2021, 12/21/2021, respectively. The HbsAb titer of Subject 3 was measured to be 490.76 mIU/ml on 8/8/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 69.19 mIU/ml on 6/26/2023 and 83 mIU/ml on 8/26/2024. Also, the HbsAg of Subject 3 was measured to be negative on 6/16/2023 and 8/26/2024.

Example 4

Subject 4 is a 58-year-old hepatitis B patient. The HbsAg of Subject 4 was measured to be positive abnormal on 9/29/2012, and the HbsAb of Subject 4 was measured to be negative on 9/29/2012. Subject 4 received BNT162b1 from Pfizer-BioNTech on 5/2/2021, 5/23/2021, 1/15/2022, 6/4/2022, respectively. The HbsAb titer of Subject 4 was measured to be 87.51 mIU/ml on 5/12/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 54.24 mIU/ml on 11/15/2022, and 29.40 mIU/ml on 8/3/2023. Also, the HbsAg of Subject 4 was measured to be negative on 8/3/2023.

Example 5

Subject 5 is a 57-year-old hepatitis B patient. The HbsAg of Subject 5 was measured to be positive abnormal on 6/25/2018, and the HbsAb of Subject 5 was measured to be ＜3.1 mIU/ml on 6/25/2018. Subject 5 received BNT162b1 from Pfizer-BioNTech on 3/29/2021, 4/18/2021, 10/11/2021 and mRNA-1273.211 from Moderna on 12/16/2022, respectively. The HbsAb titer of Subject 5 was measured to be 10.97 mIU/ml on 8/2/2021, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 24.75 mIU/ml on 2/9/2022, 22.13 mIU/ml on 8/13/2022, and 27.9 mIU/ml on 11/4/2023. Also, the HbsAg of Subject 5 was measured to be negative on 11/4/2023.

Example 6

Subject 6 is a 42-year-old hepatitis B patient. The HbsAg of Subject 6 was measured to be positive abnormal on 6/29/2017. Subject 6 received BNT162b1 from Pfizer-BioNTech on 2/8/2021, 3/1/2021, 12/28/2021 and BNT162b2 from Pfizer-BioNTech on 12/30/2022, respectively. The HbsAb titer of Subject 6 was measured to be 174 mIU/ml on 5/26/2023, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 291.89 mIU/ml on 11/29/2023, 123.02 mIU/ml on 5/10/2024. Also, the HbsAg of Subject 6 was measured to be negative on 11/29/2023 and 5/10/2024.

Example 7

Subject 7 is a 51-year-old hepatitis B patient. Subject 7 received BNT162b1 from Pfizer- BioNTech on 4/3/2021, 4/24/2021, respectively. The HbsAb titer of Subject 7 was measured to be 87 mIU/ml on 11/21/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 43.8 mIU/ml on 11/27/2023. Also, the HbsAg of Subject 7 was measured to be negative on 11/27/2023.

Example 8

Subject 8 is a 49-year-old hepatitis B patient. Subject 8 received BNT162b1 from Pfizer-BioNTech on 4/7/2021, 4/29/2021, 10/29/2021 and BNT162b2 from Pfizer-BioNTech on 11/22/2022, respectively. The HbsAb titer of Subject 8 was measured to be 134.63 mIU/ml on 12/7/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml.

Example 9

Subject 9 is a 48-year-old hepatitis B patient. The HbsAg of Subject 9 was measured to be positive abnormal on 9/17/2012, and the HbsAb of Subject 9 was measured to be negative on 9/17/2012. Subject 9 received mRNA-1273 from Moderna on 3/28/2021, 4/24/2021, 11/21/2021 and mRNA-1273.211 from Moderna on 11/19/2022, respectively. The HbsAb titer of Subject 9 was measured to be 435 mIU/ml on 3/11/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 267.52 mIU/ml on 10/19/2022, 118 mIU/ml on 10/25/2023. Also, the HbsAg of Subject 9 was measured to be negative on 3/11/2022.

Example 10

Subject 10 is a 51-year-old hepatitis B patient. The HbsAg of Subject 10 had been measured to be always positive and the HbsAb of Subject 10 had been measured to be always negative before administration of COVID-19 vaccine. Subject 10 received mRNA-1273 from Moderna on 4/7/2021, 5/5/2021, 12/9/2021, respectively. The HbsAb titer of Subject 10 was measured to be 1000 mIU/ml (which is the detection limit) on 6/21/2021, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 1000 mIU/ml on 7/18/2022, 391 mIU/ml on 1/25/2024. Also, the HbsAg of Subject 10 was measured to be negative on 1/25/2024.

Example 11

Subject 11 is a 50-year-old hepatitis B patient. The HbsAg of Subject 11 had been measured to be always positive and the HbsAb of Subject 11 had been measured to be always negative before administration of COVID-19 vaccine. Subject 11 received BNT162b1 from Pfizer-BioNTech on 5/4/2021, 5/25/2021 and mRNA-1273 from Moderna on 12/27/2021, respectively. The HbsAb titer of Subject 11 was measured to be 110.40 mIU/ml on 3/12/2022, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 158.85 mIU/ml on 3/6/2023, 491 mIU/ml on 4/8/2024. Also, the HbsAg of Subject 11 was measured to be negative on 3/12/2022, 3/6/2023 and 4/8/2024.

Example 12

Subject 12 is a 65-year-old hepatitis B patient. The HbsAg of Subject 12 was measured to be positive abnormal on 10/29/2011, and the HbsAb of Subject 12 was measured to be negative on 10/29/2011. Subject 12 received BNT162b1 from Pfizer-BioNTech on 3/31/2021, 4/21/2021 and mRNA-1273 from Moderna on 2/25/2022 and mRNA-1273.211 from Moderna on 12/23/2022, respectively. The HbsAb titer of Subject 12 was measured to be 12.35 mIU/ml on 6/17/2021, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 13.61 mIU/ml on 2/15/2022, 22.32 mIU/ml on 12/20/2022, 15.13 mIU/ml on 5/11/2023, 70.30 mIU/ml on 7/6/2023, 153.61 mIU/ml on 4/16/2024, 125 mIU/ml on 7/23/2024. Also, the HbsAg of Subject 12 was measured to be negative on 7/23/2024.

Example 13

Subject 13 is a 53-year-old hepatitis B patient. The HBV DNA (viral load) of Subject 13 was measured to be 82 mIU/ml on 12/17/2018. Subject 13 received BNT162b1 from Pfizer-BioNTech on 4/28/2021, 5/19/2021 and mRNA-1273 from Moderna on 1/7/2022, respectively. The HbsAb titer of Subject 13 was measured to be 42.37 mIU/ml on 4/19/2023, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 24.48 mIU/ml on 11/22/2023, 27.6 mIU/ml on 5/20/2024. Also, the HbsAg of Subject 13 was measured to be negative on 11/22/2023 and 5/20/2024. Further, the HBV DNA of Subject 13 was measured to be under the detection limit on 5/20/2024.

Example 14

Subject 14 is a 54-year-old hepatitis B patient. The HbsAg of Subject 14 was measured to be positive abnormal on 7/14/2012, and the HbsAb of Subject 14 was measured to be negative on 7/14/2012. Subject 14 received BNT162b1 from Pfizer-BioNTech on 03/10/2021, 04/06/2021 and BNT162b2 from Pfizer-BioNTech on 11/27/2022 and BNT162b1 from Pfizer-BioNTech on 12/26/2023, respectively. The HbsAb titer of Subject 14 was measured to be 46.90 mIU/ml on 10/24/2023, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 20.60 mIU/ml on 4/16/2024.

Example 15

Subject 15 is a 64-year-old hepatitis B patient. The HbsAg of Subject 15 was measured to be positive abnormal on 1/19/2018, and the HbsAb of Subject 15 was measured to be 3.48 mIU/ml on 1/19/2018. Subject 15 received BNT162b1 from Pfizer-BioNTech on 03/20/2021, 04/10/2021, 12/20/2021 and BNT162b2 from Pfizer-BioNTech on 10/03/2022, respectively. The HbsAb titer of Subject 15 was measured to be 66.90 mIU/ml on 11/6/2023, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml, and 88.40 mIU/ml on 05/01/2024.

Example 16

Subject 16 is a 62-year-old hepatitis B patient. The HbsAg of Subject 16 was measured to be positive abnormal on 9/5/2014, and the HbsAb of Subject 16 was measured to be negative on 9/5/2014. Subject 16 received BNT162b1 from Pfizer-BioNTech on 04/19/2021, 05/10/2021 and mRNA-1273 from Moderna on 12/17/2021 and BNT162b2 from Pfizer-BioNTech on 07/06/2023, respectively. The HbsAb titer of Subject 16 was measured to be 55.50 mIU/ml on 05/30/2024, which is the first time when the HbsAb titer was measured to be above 10 mIU/ml.

Example 17

Subject 17 is a 50-year-old hepatitis B patient. Subject 17 received mRNA-1273 from Moderna on 6/8/2021, 7/6/2021, respectively. The HbsAb titer of Subject 17 was measured to be 3.3 mIU/ml on 4/25/2023.

Example 18

Subject 18 is a 54-year-old hepatitis B patient. Subject 18 received BNT162b1 from Pfizer-BioNTech on 5/1/2021, 5/22/2021 and BNT162b2 from Pfizer-BioNTech on 12/30/2022, respectively. The HbsAb titer of Subject 18 was measured to be 6.8 mIU/ml on 1/25/2022.

Example 19

Subject 19 is a 42-year-old hepatitis B patient. Subject 19 received BNT162b1 from Pfizer-BioNTech on 4/22/2021, 5/13/2021, respectively. The HbsAb titer of Subject 19 was measured to be 6.9 mIU/ml on 12/23/2022.

Example 20

Subject 20 is a 62-year-old hepatitis B patient. Subject 20 received mRNA-1273 from Moderna on 12/1/2021, 4/28/2021, 3/31/2021, respectively. The HbsAb titer of Subject 20 was measured to be 3.4 mIU/ml on 7/29/2022.

Example 21

Subject 21 is a 59-year-old hepatitis B patient. Subject 21 received mRNA-1273 from Moderna on 3/14/2021, 4/8/2021, 12/16/2021 and mRNA-1273.211 from Moderna on 9/9/2022, respectively. The HbsAb titer of Subject 21 was measured to be 4.17 mIU/ml on 1/25/2022.

Example 22

Subject 22 is a 52-year-old hepatitis B patient. Subject 22 received mRNA-1273 from Moderna on 4/2/2021, 4/30/2021, 12/10/2021 and mRNA-1273.211 from Moderna on 11/19/2022, respectively. The HbsAb titer of Subject 22 was measured to be 3 mIU/ml on 1/23/2023.

Example 23

Subject 23 is a 43-year-old hepatitis B patient. Subject 23 received mRNA-1273 from Moderna on 3/29/2021, 4/26/2021, 1/1/2022, respectively. The HbsAb titer of Subject 23 was measured to be 4.7 mIU/ml on 2/21/2022.

Example 24

Subject 24 is a 55-year-old hepatitis B patient. Subject 24 received BNT162b1 from Pfizer-BioNTech on 05/01/2021, 05/22/2021 and BNT162b2 from Pfizer-BioNTech on 12/30/2022 and BNT162b1 from Pfizer-BioNTech on 01/10/2024, respectively. The HbsAb titer of Subject 24 was measured to be 9.29 mIU/ml on 4/10/2024.

Example 25

Subject 25 is a healthy person. The HbsAb titer of Subject 25 was measured to be 48 mIU/ml on 12/06/2018, and 48 mIU/ml on 12/12/2019.

Subject 25 received mRNA-1273 from Moderna on 04/20/2021, 05/18/2021, BNT162b1 from Pfizer-BioNTech on 11/20/2021, and BNT162b2 from Pfizer-BioNTech on 09/23/2022, respectively. The HbsAb titer of Subject 25 was measured to be 640 mIU/ml on 10/25/2021, and 631 mIU/ml on 10/31/2022.

Example 26

Subject 26 is a healthy person. The HbsAb titer of Subject 26 was measured to be 0 mIU/ml on 10/9/2012.

Subject 26 received BNT162b1 from Pfizer-BioNTech on 2/6/2021, 2/27/2021, 11/8/2021, 4/27/2022, and BNT162b2 from Pfizer-BioNTech on 10/5/2022, respectively. The HbsAb titer of Subject 26 was measured to be 52 mIU/ml on 12/15/2022, and 181 mIU/ml on 6/15/2023.

Example 27

Subject 27 is a healthy person. The HbsAb titer of Subject 27 was measured to be 16 mIU/ml on 10/31/2018.

Subject 27 received BNT162b1 from Pfizer-BioNTech on 04/03/2021, 04/24/2021, respectively. The HbsAb titer of Subject 27 was measured to be 87 mIU/ml on 11/21/2022, and 43 mIU/ml on 11/27/2023.

Example 28

Subject 28 is a healthy person. The HbsAb titer of Subject 28 was measured to be 0 mIU/ml on 04/04/2014.

Subject 28 received BNT162b1 from Pfizer-BioNTech on 04/01/2021, 04/22/2021, and mRNA-1273 from Moderna on 2022/4/6, respectively. The HbsAb titer of Subject 28 was measured to be 177 mIU/ml on 5/18/2023.

Example 29

Subject 29 is a healthy person. The HbsAb titer of Subject 29 was measured to be 0 mIU/ml on 04/01/2019.

Subject 29 received BNT162b1 from Pfizer-BioNTech on 01/29/2021, 02/15/2021, 01/02/2022, 07/06/2022, and BNT162b2 from Pfizer-BioNTech on 11/27/2022, respectively. The HbsAb titer of Subject 29 was measured to be 29 mIU/ml on 12/7/2021, 1000 mIU/ml on 11/18/2022, 364 mIU/ml on 08/23/2023.

Example 30

Subject 30 is a healthy person. The HbsAb titer of Subject 24 was measured to be 0 mIU/ml on 11/16/2018.

Subject 30 received mRNA-1273 from Moderna on 03/28/2021, 04/24/2021, 11/21/2021, and mRNA-1273.211 from Moderna on 11/19/2022, respectively. The HbsAb titer of Subject 30 was measured to be 423 mIU/ml on 03/11/2022, 267 mIU/ml on 10/19/2022, and 118 mIU/ml on 10/25/2023.

It can be concluded from Examples 1-16 that, after receiving Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine, all the hepatitis B patients have HbsAb titers above 10 mIU/ml (as summarized in Table 1 below) , indicating strong protection from hepatitis B virus.

In addition, all of Subjects 1-16 have achieved total eradication of hepatitis B viruses (as demonstrated by the negative HbsAg) , indicating clinical total recovery from hepatitis B.

Further, for each of the hepatitis B patients in Examples 1-13, during 1 year after the first time when the HbsAb titer was measured to be above 10 mIU/ml, the HbsAb titer sustained to be above 10 mIU/ml, indicating permanent immunity against hepatitis B virus.

Therefore, the Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine can be effectively used to treat hepatitis B.

Table 1

It can be concluded from Examples 17-24 that, after receiving Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine, all the hepatitis B patients have HbsAb titers above or equal to 3 mIU/ml (as summarized in Table 2 below) and continuous increasing HBsAb titer over next 12 months, indicating effective protection from hepatitis B virus. Therefore, the Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine can be effectively used to treat hepatitis B.

Table 2

It can be concluded from Examples 25-30 that, after receiving Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine, all the healthy persons have an exponential increasement in HbsAb titer, indicating remarkably enhanced protection from hepatitis B virus. Therefore, the Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine can be effectively used to prevent hepatitis B.

In summary, on the one hand, the Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine induced production of enough amount of HBsAb to eradicate hepatitis B viruses, hence, to achieve total cure of hepatitis B, and the HBsAb titers sustained long enough to provide hepatitis B patients lifetime immunity against Hepatitis B. On the other hand, the Pfizer-BioNTech COVID-19 vaccine and/or Moderna COVID-19 vaccine induced exponential increasement in HbsAb titer in healthy persons and can be used as an effective way for preventing Hepatitis B to protect the general public.

Although the specific embodiments have been described, for the applicant or a person skilled in the art, the substitutions, modifications, changes, improvements, and substantial equivalents of the above embodiments may exist or cannot be foreseen currently. Therefore, the submitted appended claims and claims that may be modified are intended to cover all such substitutions, modifications, changes, improvements, and substantial equivalents.

Claims

A method for treating or preventing hepatitis B in a subject, the method comprises:

administering effective amount of COVID-19 vaccine to the subject.
The method according to claim 1, wherein the COVID-19 vaccine comprises mRNA COVID-19 vaccine.
The method according to claim 1 or 2, wherein the COVID-19 vaccine comprises any one, any two, any three or all of BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.
The method according to any one of the preceding claims, wherein the COVID-19 vaccine comprises at least 10 μg, at least 20 μg, at least 30 μg, at least 40 μg, at least 50 μg, at least 60 μg, at least 70 μg, at least 80 μg, at least 90 μg, or at least 100 μg BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna or mRNA-1273.211 from Moderna.
The method according to any one of the preceding claims, wherein one shot, two shots, three shots, four shots or more shots of COVID-19 vaccine is/are administrated to the subject.
The method according to claim 5, wherein the interval between two adjacent shots, independently from one another, is selected from the group consisting of 1 week or longer, 2 weeks or longer, 3 weeks or longer, 1 month or longer, 2 months or longer, 3 months or longer, 4 months or longer, 5 months or longer, 6 months or longer, 7 months or longer, 8 months or longer, 9 months or longer, 10 months or longer, 11 months or longer, 1 year or longer, 1.5 years or longer, 2 years or longer, and 3 years or longer.
The method according to any one of the preceding claims, wherein the method further comprises: determining hepatitis B surface antibody (HBsAb) titer of the subject, and

administering another shot of COVID-19 vaccine, if the HBsAb titer is determined to be lower than 10 mIU/mL.
The method according to any one of the preceding claims, wherein the method further comprises: administering one or more medicines for treatment or prevention of hepatitis B, prior to, simultaneously with, and/or following the administration of COVID-19 vaccine.
The method according to claim 8, wherein at least one medicine comprises antiviral nucleotide medicine.
The method according to claim 8, wherein at least one medicine comprises entecavir, tenofovir, lamivudine, telbivudine, adefovir dipivoxil, tenofovir alafenamide and/or viread.
Use of COVID-19 vaccine in manufacturing a drug for treating or preventing hepatitis B.
The use according to claim 11, wherein the COVID-19 vaccine comprises mRNA COVID-19 vaccine.
The use according to claim 11 or 12, wherein the COVID-19 vaccine comprises any one, any two, any three or all of BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna and mRNA-1273.211 from Moderna.
The use according to any one of the claims 11-13, wherein the COVID-19 vaccine comprises at least 10 μg, at least 20 μg, at least 30 μg, at least 40 μg, at least 50 μg, at least 60 μg, at least 70 μg, at least 80 μg, at least 90 μg, or at least 100 μg BNT162b1 from Pfizer-BioNTech, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna or mRNA-1273.211 from Moderna.