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

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 × 10 or 1 × 10 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 × 10 vp and 956.6 (595.8 to 1535.8) for 1 × 10 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 10 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 10 vp. A 1-dose regimen of 1 × 10 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.