The Ad26.ZIKV.001 vaccine against Zika virus had satisfactory safety and immunomodulatory properties according to the results of a phase I trial, published in Annals of internal medicine.
A group of 100 healthy adult volunteers was recruited from two centers and randomly assigned to receive two low doses (LD; 5 × 10).10 viral particles), 1 LD and 1 placebo (0.9% saline), 2 high doses (HD; 1 x 10).11 viral particles), 1 HD and 1 placebo, or 2 placebo injections (ClinicalTrials.gov: NCT03356561). The two-dose vaccines were administered by intramuscular injection 56 days apart. Participants were followed for one year for safety and interaction outcomes.
At baseline, the mean age of participants was 29 years (range, 18-50) years, 55% were women, and 72.4% were white.
After the first dose, 75% of LD, 88% of HD, and 45% of placebo recipients reported adverse events. Grade 3 systemic events were reported by 2 LD and 5 HD recipients, and one HD recipient had a grade 4 pyrexia event.
After the second dose, adverse events were reported by 58%, 56%, and 39% of the LD, HD, and placebo cohorts, respectively. No serious adverse events related to the study were observed and no participant withdrew from the trial due to adverse events.
28 days after the first dose, 88% of the LD and 94% of the HD groups had seroconverted. At 14 days after the second dose, the LD and HD groups had geometric means of 823.4 (95% CI, 414.3% -1636.6%) and 961.5 (95% CI, 552.7% -1672.9%), respectively. At day 365, 56% of the single-dose LD and 88% of the HD groups had a mean detectable log titer compared to 80% and 87.0% of the double-dose groups, respectively.
At 28 days, interferon (IFN)-g responses were observed among 23 of 25 participants evaluated for cellular immunogenicity. This immune response was maintained within 1 year with detection of membrane-specific, but not membrane-specific CD4+ and CD8+ T-cell responses.
Antibodies from vaccinated individuals, or unvaccinated sham controls, collected on day 85 were transferred to mice. After Zika virus was challenged, all mice that received the dummy antibodies showed virus infection, and the mice that received antibodies were protected from the vaccinated individuals. Protected mice had a mean geometric titer of 16.1, which is higher compared to unprotected mice (5.5).
This study was limited by the fact that the study was not conducted in a Zika virus-endemic area, and additional site-specific trials are needed.
The safety and immunogenicity profile of the Ad26.ZIKV.001 vaccine indicated strong and durable protection against Zika virus for up to 1 year.
Disclosure: Several authors have declared industry affiliation. Please refer to the original article for a full list of disclosures.
Salch, NC, Stevenson K, Williams K, et al. A phase I double-blind, randomized, placebo-controlled study of Ad26.ZIKV.001, an Ad26 vector Zika virus vaccine. Ann med trainee. Published online February 16, 2021. doi: 10.7326 / M20-5306