PreHevbrio: the first approved 3-antigen hepatitis B vaccine

ABSTRACT

Introduction

Hepatitis B remains a major cause of death and morbidity worldwide. Universal childhood immunization programs have been very successful, but many adults remain unprotected or are not optimally protected. PreHevbrio [Hepatitis B Vaccine (recombinant)] is a highly immunogenic 3-antigen (S/pre-S1/pre-S2) hepatitis B vaccine (3A-HBV) that recently received marketing authorization in the United States (2021), the European Union, United Kingdom (2022 – brand name PreHevbri), and Canada (2022– brand name PreHevbrio) for the prevention of infection caused by all known subtypes of the hepatitis B virus and the delta virus in adults 18 years and older.

Areas covered

This review details the development of 3A-HBV and summarizes the results of the phase 3 clinical trials that support its immunogenicity and safety in adults.

Expert Opinion

3A-HBV is highly immunogenic in adults of all ages, including older adults and subgroups that respond sub-optimally to conventional single S-antigen hepatitis B vaccines (1A-HBV), such as those with obesity, type 2 diabetes, and smokers. 3A-HBV provides higher seroprotection rates after each vaccination compared to conventional 1A-HBV vaccines, allowing for more rapid protection. The higher overall immunogenicity is also reflected in more durable seroprotection years after vaccination, as supported by a follow-up study to one of the phase 3 studies.

KEYWORDS:

• Hepatitis B virus
• vaccine
• HBsAg
• pre-S1
• pre-S2
• surface antigen
• anti-HBs antibody
• seroprotection

Article highlights

• Almost 300 million people worldwide are chronically infected with hepatitis B.

• Approximately 90% of the individuals with chronic HBV infection are not aware of their status, allowing for ongoing transmission to susceptible populations.

• In North America and Europe, most new infections occur in adults.

• Conventional single S-antigen HBV vaccines (1A-HBV) adjuvanted with alum have reduced immunogenicity in adults.

• Effective and fast-acting adult HBV vaccines are required to maximize the benefit of expanded adult vaccination rates, as supported by the recent adoption of a universal hepatitis B vaccination recommendation by the Advisory Committee on Immunization Practices (ACIP) in the United States for adults 19–59 years.

• PreHevbrio is a highly immunogenic 3-antigen (S/pre-S1/pre-S2) HBV vaccine (3A-HBV) approved in the United States (2021), Europe (2022), and Canada (2022) for the prevention of all known subtypes of HBV.

• In phase 3 clinical trials, 3A-HBV demonstrated improved seroprotection in adults ≥45 years old and higher rates of seroprotection in adults ≥18 years old after each vaccination compared to 1A-HBV (Engerix-B).

• 3A-HBV was initially approved in Israel in 2000 (Brand name: Sci-B-Vac) and has a 20-year post-marketing safety history, with estimated 750,000 individuals vaccinated.

• As the only approved 3-antigen HBV vaccine, PreHevbrio/PreHevbri has the potential to be a meaningful new tool in the fight to reduce the risk of HBV infection in adults, toward achieving hepatitis B elimination by 2030.

Declaration of interest

T Vesikari has received funding for PROTECT and CONSTANT studies from VBI Vaccines, Inc., through the Nordic Research Network Oy company of which he owns stock. J Langley received funding from VBI Vaccines for PROTECT and CONSTANT studies. V Popovic is an officer and owns shares of VBI Vaccines. F Diaz-Mitoma is an officer and owns shares of VBI Vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by VBI Vaccines, Inc.