When It Comes to Hep B Vaccine, Three Antigens May Be Better Than One

A three-antigen hepatitis B vaccine (3A-HBV) induced higher hepatitis B surface antibody (anti-HB) concentrations and seroprotection versus the single-antigen vaccine (1A-HBV) in a phase III trial.

Healthy adults ages 18-45 had higher mean serum anti-HB concentrations after a three-dose regimen of 3A-HBV, and seroprotection rates were noninferior versus a three-dose regimen of 1A-HBV, reported Francisco Diaz-Mitoma, MD, PhD, of VBI Vaccines in Ottawa, Canada, and colleagues.

“The rapid induction of protective antibody levels in more than 90% of participants after two doses of 3A-HBV in the current study is noteworthy, particularly for populations in whom rapid seroprotection is required,” the authors wrote in JAMA Network Open.

They noted several limitations to conventional yeast-derived 1A-HBV, namely that they have a “prolonged time to achieve seroprotection,” with only 30-40% of adults seroprotected after two doses and 10% failing to achieve seroprotection after a full three-dose regimen. The authors also discussed an “age-dependent decline” in response rate, with seroprotection rates dropping to below 75% after the age of 40.

The recombinant 3A-HBV, Sci-B-Vac, contains three HBV surface antigens — pre-S1, pre-S2 and S — while the 1A-HBV only contains the small S antigen (HBsAg), they added. A prior phase III trial, PROTECT, found the 3A-HBV to be “highly immunogenic for adults, including older adults with well-controlled chronic conditions,” the authors noted.

For the current study, Diaz-Mitoma and colleagues examined data from 2,838 healthy adults ages 18-45 who were vaccinated at 37 sites in Finland, the U.K., Belgium, Germany, Canada, and the U.S. from December 2017 to October 2019. They were randomized 4:1 to receive three intramuscular injections of 3A-HBV (10 µg) or 1A-HBV (20 µg) at days 0, 28, and 168. There were three 3A-HBV lot groups to determine lot-to-lot manufacturing consistency.

The main outcome assessed the immunogenicity of the 3A-HBV compared to the 1A-HBV, evidenced by mean serum concentration of anti-HB concentrations 4 weeks following the third injection. Noninferiority of pooled seroprotection rates was a secondary outcome.

Patients had a mean age of 34, most were white (92%) and almost 60% were women. Most had a BMI of under 30 (82%), 62% did not smoke, and 93% had minimal to no alcohol use.

Anti-HB concentrations rose between the second and third doses of both vaccines, though antibody levels peaked at day 196 in the 3A-HBV group and was 3.5-fold greater than antibody levels among those who received 1A-HBV.

After three doses, the pooled seroprotection rate of all three groups who received the 3A-HBV (99%, 95% CI 98.7%-99.6%) was noninferior to the 1A-HBV group (95%, 95% CI 92.7%-96.4%).

About 68% of participants in the 3A-HBV group and 60% in the 1A-HBV group reported systemic adverse events (AEs) within 7 days of any injection — the median duration of symptoms was about 2 days. Serious AEs were reported in 42 participants (2%) in the 3A-HBV group and four participants (0.4%) in the 1A-HBV group. The 3A-HBV was associated with a greater incidence of local AEs within 1 week (erythema, pain, pruritus).

While there were no vaccine-related serious AEs during the study, mild congenital ankyloglossia in an offspring of a participant in the 3A-HBV group that was deemed possibly related to study vaccine occurred after the study. One patient had a sudden cardiac death after 1 week of receiving the 3A-HBV, though the participant had a prior history of cardiovascular disease.

One limitation researchers acknowledged was using seroprotection as an immunological surrogate of clinical protection against HBV infection. The authors noted that the 3A-HBV is licensed in Israel, but has yet to receive regulatory approval in the U.S.