NEW YORK (Reuters Health) – A tri-antigenic hepatitis B vaccine (TAV) effectively prevented hepatitis B virus (HBV) infection in adults, was somewhat more effective than a mono-antigenic vaccine (MAV) comparator, but had higher side effect rates in a phase 3 multicenter trial.
“Unfortunately, vaccination of adults with the current standard single antigen, yeast-derived HBV vaccines have important limitations, including reduced immunogenicity in older adults, obese individuals, smokers, adults with diabetes, and chronic kidney or liver failure patients, and a prolonged time to protection,” Dr. Francisco Diaz-Mitoma, chief medical officer at the study funder, VBI Vaccines in Cambridge, Massachusetts, told Reuters Health by email.
“The…combination of the 3-antigen conformation, compared to a single S antigen conformation, and the mammalian cell derivation, compared to yeast-derived vaccines, enables TAV to elicit a robust immune response comparable to that of the wild type virus in adults,” he said.
As reported in The Lancet Infectious Diseases, 1,607 HBV-seronegative adults in the U.S., Finland, Canada and Belgium were randomly assigned to TAV or MAV. Participants, some with well controlled chronic conditions, were distributed across age cohorts of 18-44 (18.6%), 45-64 (44.6%), and 65 and older (36.8%).
Both vaccines were given as an intramuscular dose (1 mL): TAV (10 mcg; Sci-B-Vac, VBI Vaccines) or MAV (20 mcg; Engerix-B, GlaxoSmithKline Biologicals) on days 0, 28, and 168, with a total of six study visits and 24 weeks of follow-up after the third vaccination.
The co-primary outcomes were to show non-inferiority of the seroprotection rates (SPRs) four weeks after the third vaccination with TAV versus MAV in the per-protocol set of participants, as well as superiority in adults 45 years and older who received at least one vaccination.
SPR was defined as the percentage of participants attaining anti-HBs titers of 10 mIU/mL or higher.
Non-inferiority of TAV to MAV was concluded if the lower limit of the 95% CI for the between-group difference was greater than -5%.
In the per-protocol set, SPR was 91.4% in the TAV group versus 76.5% in the MAV group, showing non-inferiority.
In participants 45 and older, SPR was 89.4% in the TAV group versus 73.1% in the MAV group, showing superiority in the full analysis set.
However, TAV was associated with higher rates of mild or moderate injection site pain (63.2% vs. 36.3%), tenderness (60.8% vs. 34.8%), and myalgia (34.7% vs. 24.3%).
The rest of the safety profile was similar between groups.
Dr. Diaz-Mitoma said the findings show the TAV’s “potential to overcome some of the limitations of current HBV vaccination and be a meaningful additional intervention in the fight against hepatitis B.”
Dr. Blythe Adamson, Founder, Infectious Economics and Principal Quantitative Scientist at Flatiron Health in New York City commented in an email to Reuters Health, “Hep B vaccines are important for everyone and we have many safe and effective choices available. There are three single-antigen hep B vaccines on the market in the United States today plus a few more vaccines that prevent a combination of diseases including hep B.”
“With regard to Sci-B-Vac, the phase 3 trial results were modest, suggesting that it works well but it may not be better than its competitors already available in the US. Sci-B-Vac was slightly more effective than Engerix-B, but had more side effects.”
The study was funded by VBI Vaccines. Dr. Diaz-Mitoma and five coauthors are employees and the other coauthors received funds from the company to conduct the study.
SOURCE: https://bit.ly/2RWztbP and https://bit.ly/2TfQ7DB The Lancet Infectious Diseases, online May 11, 2021.
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