In the search for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults at risk for infection, a new international study looked at the effectiveness and safety of a 3-antigen versus a single-antigen HBV vaccine.

In research published in JAMA Network Open, the investigators sought to do the following:

• Demonstrate manufacturing equivalence of a 3-antigen (3A-) HBV vaccine

• Evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV versus single-antigen (1A-) HBV after two and three vaccine doses

• Compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines.

The phase lll, double-blind, randomized clinical trial was performed at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. The 2,838 healthy adults aged 18 to 45 years, of whom 57.8% were women and 91.5% were white, were randomized to one of three 3A-HBV groups or one control group receiving 1A-HBV and were followed for 48 weeks after the first vaccination.

Study subjects received intramuscular administration of 3A-HBV (10 g) or 1A-HBV (20 g) on Days 0, 28, and 168. Researchers were focused on the geometric mean concentration (GMC) of serum hepatitis B surface antibodies (anti-HBs) and the proportion of participants achieving seroprotection.

Results demonstrated 3A-HBV lot-to-lot consistency, as the 3-sided 95% CIs for each pairwise comparison for the anti-HB GMC ratios were within 0.67 and 1.50 (e.g., adjusted GMC ratio, lot A vs. lot B: 0.82; 95% CI, 0.67-1.00; lot A vs. lot C: 0.95; 95% CI, 0.78-1.15; lot B vs. lot C: 1.16; 95% CI, 0.95-1.41).

The SPR of the pooled 3A-HBV was found to be noninferior to 1A-HBV and higher than 1A-HBV after two vaccinations at Day 168 (90.4% [95% CI, 89.0%-91.8%] vs. 51.6% [95% CI, 47.5%-55.6%]) and three vaccinations at Day 196 (99.3% [95% CI, 98.7%-99.6%] vs. 94.8% [95% CI, 92.7%-96.4%]).

In fact, the mean GMC of anti-HBs with 3A-HBV was 7.9 times higher after two vaccinations at Day 168 and 3.5 times higher after three vaccinations at Day 196 compared with 1A-HBV (after two vaccinations, 3A-HBV: GMC, 118.7 mIU/mL; 95% CI, 108.0-129.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: GMC, 15.0 mIU/mL; 95% CI, 12.9-17.5 mIU/mL; SE, 1.0 mIU/mL; after three vaccinations, 3A-HBV: GMC, 5442.4 mIU/mL; 95% CI, 4967.0-5963.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: 1567.2 mIU/mL; 95% CI, 1338.0-1834.0 mIU/mL; SE, 1.0 mIU/mL).

The authors note that rates of local and systemic reactogenicities were higher with 3A-HBV compared with 1A-HBV (local: 1,805 of 2,124 [85.0%] vs. 469 of 712 [65.9%]; systemic: 1445 [68.0%] vs. 428 [60.1%]). Still, they report, vaccine discontinuation due to adverse events (AEs) was uncommon, and serious AEs were infrequent, reported in 42 participants (2.0%) and three participants (0.4%) in the 3A-HBV and 1A-HBV groups, respectively.

"In this study, consistently higher antibody concentrations and SPRs were found with 3A-HBV after two and three doses vs 1A-HBV in adults aged 18 to 45 years old," the researchers conclude. "The safety and efficacy of 3A-HBV shows its usefulness for the prevention of hepatitis B in young healthy adults."

Background information in the article indicates that vaccination rates against HBV, the leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, remain low in adults. "Adults who were not immunized as infants remain at risk of HBV infection. Noncompletion of a 3-dose vaccine over 6 months is frequent, and a recent study found that a 2-dose vaccine has better adherence than a 3-dose vaccine among U.S. adults," the article notes.

The report states that HBV infections in the U.S. are highest among persons aged 30 to 49 years, with rates of 33.2% of those aged 25 to 39 years, 32.0% of those aged 45 to 54 years, and 27.6% of those aged 55 years and older in 2016. Most in need of an HBV vaccine that ensures rapid seroprotection are healthcare workers, military personnel, and travelers to endemic regions, the authors write.

The researchers also point out that single-antigen (1A), yeast-derived HBV vaccines have significant limitations, including prolonged time to achieve seroprotection, with only 30% to 40% of adults seroprotected after two doses. At least 10% of all adults fail to achieve seroprotection after a 3-dose schedule and are considered nonresponders to HBV vaccination, they add.

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