番茄社区

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 .

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, , 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, , 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.

"Regardless of age, diabetic status, or BMI, the 3-antigen HBV vaccine candidate induced anti-HBs titers that were 4-8x higher than those induced by Engerix-B," Diaz-Mitoma told 番茄社区.

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.

"Following these positive results, we have been working with regulatory agencies in North America and Europe to support their review of our marketing authorization applications," Diaz-Mitoma said.

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