A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine

Abstract

Background: Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available.

Objective: To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate.

Design: Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561).

Setting: United States.

Participants: 100 healthy adult volunteers.

Intervention: Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 10¹⁰ or 1 × 10¹¹ viral particles (vp), or placebo.

Measurements: Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model.

Results: All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 10¹⁰ vp and 956.6 (595.8 to 1535.8) for 1 × 10¹¹ vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 10¹⁰ vp and 87.0 (CI, 29.3 to 258.6) for 1 × 10¹¹ vp. A 1-dose regimen of 1 × 10¹¹ vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model.

Limitation: The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population.

Conclusion: The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges.

Primary funding source: Janssen Vaccines and Infectious Diseases.