Three Phase 1 human clinical trials evaluating the efficacy of an Army-developed Zika purified inactivated virus (ZPIV) vaccine have shown it to be safe and well tolerated, according to a study published in The Lancet. The three single-center studies were performed to address a specific issue either on vaccine dosage, schedule or background immunity.
One of the studies assessed the effect of pre-existing flavivirus immunity conferred by priming with a licensed yellow fever. Another study assessed the safety and immunogenicity of three ZPIV doses (2.5 μg, 5.0 μg, and 10.0 μg). The last study assessed dosing schedules: two doses separated by 2 weeks, 4 weeks, or as one dose. Over the course of the study, 67 participants were vaccinated (55 with ZPIV and 12 with placebo) on Days 1 and 29 and were followed up to Day 57 for analysis. Participants were men and women (mean age: 31.5 years) who had no history or serological evidence of flavivirus infection or vaccination. Adverse events (AEs) or systemic reactogenic events were recorded for 1 week after vaccination and all other AEs were recorded for 28 days after each vaccination.
Overall, 56 (84%) participants reported one or more AEs after the first, second, or both doses. There were 43 (64%) participants who reported mild local injection-site events, while 2 (3%) had moderate injection-site events. In regard to systemic reactogenic events after vaccination, in 33 (49%) participants those reactions were mild, in 10 (15%) they were moderate, and 1 (2%) had a severe event, but the authors deemed that AE to be unattributable to the vaccination. In nearly all vaccinated participants, ZPIV produced neutralizing antibody responses at 2 or 4 weeks after the last dose. By Day 57, 92% of vaccine recipients developed strong antibody responses against Zika virus, with levels of virus-neutralizing antibodies in the blood exceeding the protective thresholds observed in prior animal models. Also encouraging is that when the researchers injected mice with antibodies from study participants who received the vaccine, the mice were protected against later exposure to Zika virus, unlike mice who were injected with antibodies from placebo participants.
While the studies are ongoing, the authors are enthused by the early results. They believe the research’s strength is the coordination of the three clinical sites which were held in both academic and government organizations and the inclusion of immunogenicity for the vaccine by harmonized methods in one laboratory. The study’s limitations were acknowledged to be those associated with short-term follow-up, but data from long-term follow-up are expected to be published once available.