Nonresponders to primary immunization against hepatitis B virus (HBV) may be revaccinated effectively with additional vaccine doses, of which Fendrix and HBVaxPro-40 had higher responder rates vs other vaccine regimens, according to study results published in The Lancet.
The investigators of this open-label, parallel-group, randomized controlled study sought to determine which of the 3 alternative revaccination regimens (Fendrix, Twinrix, and HBVaxPro-40) is the most effective to induce protective immunity in healthy adults who do not respond to the initial vaccine.
The study included 480 healthy adults, 18 to 80 years of age, from 16 different health centers in the Netherlands, who reported vaccine nonresponse after a primary vaccination series with 3 doses of a recombinant vaccine against HBV (HBVaxPro-10 or Engerix-B). Participants were randomly assigned to receive a vaccination series with either repeated initial vaccination as control (n=124), Fendrix 20 μg (n=124), Twinrix 20 μg (n=118), or HBVaxPro-40 40 μg (n=114). Revaccination schedules were all identical and a single dose was administered intramuscularly at 0, 1, and 2 months; hepatitis B surface antibody titers were sampled at 0, 1, 2, and 3 months. The primary end point was the proportion of responders (defined as having hepatitis B surface antibody titers ≥10 IU/L) reported at 3 months. Secondary end points included geometric mean titers measured at 1, 2, and 3 months and the number of revaccinations needed to reach serological response at each time point. Participants were asked to record any adverse events or possible injection site reactions.
Potential confounders did not differ between groups; furthermore, the intervals between vaccination doses and titer measurements were similar between primary and revaccination series. The proportion of responders increased with each additional dose, as did geometric mean titer measurements. After the third revaccination, serological response was observed in 67% of the control group (95% CI, 57.9-75.1); 87% of the Fendrix group (95% CI, 79.9-92.4); 80% of the Twinrix group (95% CI, 71.3-86.5); and 83% of the HBVaxPro-40 group (95% CI, 75.2-89.7). In adjusted analyses, the difference in responder rate was significant for the HBVaxPro-40 (P =.0204) and the Fendrix groups (P =.0006) vs the control group, but not for Twinrix vs controls (P =.0846). Myalgia and injection site pain were the most frequently reported reactions, and only a single serious adverse event (unrelated to the vaccine) was reported in the Fendrix group.
A limitation to the study was the lack of data on long-term protection after revaccination. Certain centers did not report the number of candidates who declined to participate, and therefore data related to the external validity may have been affected. The minimum interval between first and second dose was set at 3 weeks instead of 4; even though there was a limited number of participants with a minimal interval between doses — and evenly distributed between groups — this may have led to an overestimation of nonresponse.
Most nonresponders after primary vaccination reached protective antibody concentrations following a series of 3 revaccinations. The investigators suggest that Fendrix or HBVaxPro-40 showed superior immunogenicity and was more effective at inducing HBV antibody response in the revaccination of healthy nonresponders.
Raven SFH, Hoebe CJPA, Vossen ACTM, et al. Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial [published online October 16, 2019]. Lancet. doi: 10.1016/S1473-3099(19)30417-7