Phase I Trial Of An Adenovirus Vector Vaccine for Zika Virus Shows High Immunogenicity And Safety

The Ad26.ZIKV.001 vaccine against the Zika virus had a satisfactory immunogenicity and safety profile according to results from a phase 1 trial, published in Annals of Internal Medicine.

A group of 100 healthy adult volunteers were recruited from 2 centers and randomly assigned to receive 2 low doses (LD; 5×10¹⁰ viral particles), 1 LD and 1 placebo (0.9% saline), 2 high doses (HD; 1×10¹¹ viral particles), 1 HD and 1 placebo, or 2 placebos injections (ClinicalTrials.gov: NCT03356561). Two-dose vaccines were administered intramuscularly 56 days apart. Participants were followed for 1 year for safety and reactogenicity outcomes.

At baseline, the median age of participants was 29 (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 1 HD recipient had a grade 4 pyrexia event.

Following 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.

At 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 mean titers 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 LD and 88% of the HD groups had detectable median log titers compared with 80% and 87.0% of the double dose groups, respectively.

At 28 days, interferon (IFN)-g responses were observed among 23 of the 25 participants who were assessed for cellular immunogenicity. This immune response was maintained through 1 year with envelope-specific, but not membrane-specific IFN-g-secreting CD4+ and CD8+ T-cell responses detected.

Antibodies from vaccinated individuals, or unvaccinated placebo controls, collected at day 85 were transferred to mice. After being challenged with the Zika virus, all mice who received placebo antibodies exhibited viremia and mice who received antibodies from vaccinated individuals were protected. The protected mice had geometric mean titers of 16.1, which was higher compared with unprotected mice (5.5).

This study was limited by not conducing the study in a Zika virus endemic region, and additional site-specific trials are needed.

The safety and immunogenicity profile resulting from the Ad26.ZIKV.001 vaccine indicated a potent and durable protection against Zika virus for up to 1 year.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Salisch N C, Stephenson K E, Williams K, et al. A double-blind, randomized, placebo-controlled phase 1 study of Ad26.ZIKV.001, an Ad26-vectored anti–Zika virus vaccine. Ann Intern Med. Published online February 16, 2021. doi:10.7326/M20-5306