About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Should PreHevbrio be recommended as an option for adults recommended for hepatitis B (HepB) vaccination?
Population: Adults greater than or equal to 18 years of age
Intervention: PreHevbrio – 3 doses over 6 months
Comparison(s): Existing HepB vaccines licensed for adults in the US (Twinrix, Engerix-B, Recombivax-HB, Heplisav-B)*
Outcomes:
Hepatitis B virus (HBV) infection (CRITICAL)
Serious adverse events (CRITICAL)
Mild adverse events (IMPORTANT but not critical)
*Of the adult HepB vaccines licensed in the United States, the included studies had only Engerix-B as a comparator
Background
On November 3, 2021, ACIP voted to recommend universal adult HepB vaccination for all adults aged 19 through 59 years. Prior to the February 23, 2022 ACIP meeting, four HepB vaccines were recommended for use by ACIP (Engerix-B, Recombivax-HB, Twinrix, Heplisav-B). FDA approval for PreHevbrio was completed on November 30, 2021. Safety and immunogenicity data for PreHevbrio was presented by the vaccine manufacturer (VBI Vaccines, Delaware, USA), to ACIP on January 12, 2022.
The purpose of this EtR was to consider the addition of a new 3-antigen HepB vaccine candidate (PreHevbrio) as an option for prevention of hepatitis B on the CDC adult immunization schedule (starting in 2023). Based on key similarities with the approved single-antigen adult HepB vaccines, including immunogenicity, dosing schedule, mechanism, and safety profile, no ACIP vote was required for this action, and the EtR Framework was presented as an informational session on February 23, 2022.
Note: the safety and effectiveness of PreHevbrio have not been established in adults on hemodialysis. In addition, there are no adequate and well-controlled studies of PreHevbrio in pregnant women. Available human data on PreHevbrio administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Persons on hemodialysis, pregnant persons and persons who are breastfeeding are not discussed in the Evidence to Recommendations Framework.
Additional background information supporting the ACIP recommendations on the use of PreHevbrio vaccine can be found in the relevant publication of the recommendation referenced on the ACIP website.
Problem
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| Is the problem of public health importance?
(Is the prevention of hepatitis B a problem of public health importance?)
|
Yes | In 2021, ACIP approved universal HepB vaccine recommendations for adults ages 19 through 59 years.
An additional HepB vaccine that is safe and non-inferior to existing ACIP-approved HepB vaccines could be a beneficial adjunct in achieving HHS goals of eliminating hepatitis B as a public health threat in the United States by 2030.
|
Benefits and Harms*
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| How substantial are the desirable anticipated effects?
For prevention of HBV infection (seroprotection), how substantially different are the desirable anticipated effects of PreHevbrio compared with Engerix-B?
|
Minimal | The evidence suggests that seroprotection conferred by PreHevbrio is non-inferior (little or no difference) compared with seroprotection conferred by Engerix-B. | |
| How substantial are the undesirable anticipated effects?
For the outcomes of serious and mild adverse events, how substantially different are the undesirable anticipated effects of PreHevbrio compared with Engerix-B?
|
Minimal | PreHevbrio may result in little to no difference in serious adverse events when compared with serious adverse events resulting from Engerix-B.
PreHevbrio may result in little to no difference in mild adverse events when compared with mild adverse events resulting from Engerix-B.
|
|
| Do the desirable effects outweigh the undesirable effects?
Does the balance between desirable effects and undesirable effects favor PreHevbrio or Engerix-B?
|
Favors both | See GRADE Tables | |
| What is the overall certainty of this evidence for the critical outcomes? | Probably not important uncertainty | See GRADE Tables |
Equity
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| What would be the impact on health equity?
What would be the impact of the PreHevbrio compared to Engerix-B on health equity?
|
Probably no impact | PreHevbrio provides an additional option to existing approved adult HepB vaccines. |
Based on similarities of dosage schedule, adjuvant, and vaccine mechanism, ACIP Hepatitis Work Group perceived that the domains of Values, Acceptability, Resource Use, and Feasibility for PreHevbrio are comparable with Values, Acceptability, Resource Use and Feasibility of Engerix-B.
Balance of consequences
Desirable consequences clearly outweigh undesirable consequences in most settings.
Recommendation
PreHevbrio may be used as a HepB vaccine in persons aged ≥18 years recommended for vaccination against HBV infection.
Additional Considerations
Persons on hemodialysis, pregnant persons and persons who are breastfeeding are not discussed in this Evidence to Recommendations Framework. The safety and effectiveness of PreHevbrio have not been established in adults on hemodialysis. There are no adequate and well-controlled studies of PreHevbrio in pregnant women. Available human data on PreHevbrio administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Data are not available to assess the effects of PreHevbrio on the breastfed infant or on milk production/excretion.
View the complete list of EtR Frameworks
- Vesikari T, Langley JM, Segall N, et. al. Immunogenicity and safety of a tri-antigenic hepatitis B vaccine, Sci-B-Vac®, compared with a mono-antigenic HepB vaccine, Engerix-B®, in adults: The PROTECT randomized clinical trial. The Lancet Infectious Diseases. 2021.
- Vesikari T, Finn A, van Damme P, et al. Immunogenicity and safety of a 3-antigen hepatitis B vaccine vs a single-antigen hepatitis B vaccine: a phase 3 randomized clinical trial. JAMA Network Open. 2021; 4(10).
- Diaz-Mitoma F, Popovic V, Spaans JN. Assessment of immunogenicity and safety across two manufacturing lots of a 3-antigen hepatitis B vaccine, Sci-B-Vac®, compared with Engerix-B® in healthy Asian adults: A phase 3 randomized clinical trial. Vaccine. 2021 Jun 29;39(29):3892-3899. Epub 2021 Jun 8.
- Raz R, Koren R, Bass D. Safety and immunogenicity of a new mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in adults. Isr Med Assoc J. 2001 May;3(5):328-32.
- Esaulenko EV, Yakovlev AA, Volkov GA, et. al. Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation. Clin Infect Dis. 2021 Nov 2;73(9).
- Etzion O, Novack V, Perl Y, et. al. Sci-B-VacTM Vs ENGERIX-B Vaccines for Hepatitis B Virus in Patients with Inflammatory Bowel Diseases: A Randomised Controlled Trial. J Crohns Colitis. 2016 Aug;10(8):905-12. Epub 2016 Feb 29.
- Yap I, Guan R, Chan SH. Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines. J Gastroenterol Hepatol. 1995 Jan-Feb;10(1):51-5.
- Murthy N, Wodi AP, Bernstein H, McNally V, Cineas S, Ault K. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:229–233.
- GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2021. Available from gradepro.org.
- Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020.