A safe and well-tolerated Zika purified inactivated virus (ZPIV) vaccine requires 2 doses for immunogenicity, according to study results recently published in the Lancet Infectious Diseases.
The Zika virus epidemic in 2015-2016 prompted the urgent development for a safe and effective Zika vaccine. During this epidemic, thousands of children had prenatal Zika virus infection, which resulted in severe developmental problems once they were born. One vaccine (ZPIV) moved to clinical trials quickly, and results showed that ZPIV was safe and immunogenic at ≤8 weeks’ follow-up when 2 doses were given at weeks 0 and 4; however, different ZPIV vaccine schedules for optimization had not been explored. Therefore, this single-center, double-blind, sequential-group, randomized, placebo-controlled phase 1 study assessed the safety and immunogenicity of ZPIV in humans at ≤52 weeks of follow-up when given via standard or accelerated vaccination schedules (ClinicalTrials.gov identifier: NCT02937233).
Between 2016 and 2017, investigators included 36 healthy participants aged 18 to 50 years in the study and sequentially enrolled them into one of 3 groups: standard regimen (ZPIV given at weeks 0 and 4), accelerated regimen (ZPIV given at weeks 0 and 2), or single-dose regimen (ZPIV given only at week 0). They designated 12 participants to each group and randomly assigned them to receive vaccine (n=10 in each group) or saline placebo (n=2 in each group). The primary endpoint of this study was safety up to day 364 postdose. The secondary endpoints of this study were proportion of participants with positive humoral immune responses (defined as 50% microneutralization titer [MN50] ≥100) and geometric mean MN50 at observed peak response (defined as the highest neutralizing antibody level observed for an individual participant across all timepoints). The safety population included all participants who received ≥1 dose of ZPIV or placebo.
Results suggested that ZPIV was safe and well tolerated at ≤52 weeks’ follow-up, and that immunogenicity required 2 doses. No serious or grade 3 treatment-related adverse events were reported during this study. Among the 30 participants who received the vaccine, the most common adverse events were injection-site pain (24 participants [80%]), fatigue (16 participants [53%]), and headache (14 participants [46%]).
Researchers found a positive response at observed peak titer in all participants in the standard regimen group, 8 participants (80%) in the accelerated regimen group, and no participants in the single-dose regimen group who received vaccine. The geometric mean of all individual subjects’ observed peak values was 1153.9 (95% CI, 455.2-2925.2) in the standard regimen group, 517.7 (95% CI, 142.9-1875.6) in the accelerated regimen group, and 6.3 (95% CI, 3.7-10.8) in the single-dose regimen group. For all groups (and vaccine schedules), geometric mean titers (GMT) peaked 2 weeks after final vaccination and declined to <100 by week 16.
At week 28, investigators observed a positive response in 1/8 of participants (13%) who received vaccine in the standard regimen and no participants who received vaccine in the accelerated (n=7) or single-dose (n=10) regimen groups. The GMT for this time point was 13.9 (95% CI, 3.5-55.1) in the standard regimen group, 6.9 (95% CI, 4-11.9) in the accelerated regimen group, and undetectable in the single-dose regimen group. Researchers observed no difference in observed peak GMTs between the standard (4-week) and accelerated (2-week) regimens (P =.4494).
Limitations of this study included no randomization between groups, small sample sizes, and a lacking variation in demographic characteristics (ie, most of the study population was female, White, and non‑Hispanic).
Overall, the study authors concluded, “[o]ngoing studies of a late ZPIV boost (NCT02963909) and higher ZPIV doses (NCT02952833) will provide more information about whether the ZPIV regimen can be optimized further.”
Stephenson KE, Tan CS, Walsh SR, et al. Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial [published online May 6, 2020]. Lancet Infect Dis. doi: 10.1016/S1473-3099(20)30085-2