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

作者：Nadine C. Salisch, Kathryn E. Stephenson, Kristi L. Williams, Freek Cox, Leslie van der Fits, Dirk Heerwegh, Carla Truyers, Marrit N. Habets, Diane G. Kanjilal, Rafael A. Larocca, Peter Abbink, Jinyan Liu, Lauren Peter, Carlos Fierro, Rafael A. De La Barrera, Kayvon Modjarrad, Roland Zahn, Jenny Hendriks, Conor P. Cahill, Maarten Leyssen, Macaya Douoguih, Johan Van Hoof, Hanneke Schuitemaker, Dan H. Barouch · 发表于：Annals of Internal Medicine · 年份：2021 · DOI：10.7326/m20-5306 · 被引用次数：84 · 研究领域：Mosquito-borne diseases and control、Viral Infections and Outbreaks Research、Virology and Viral Diseases

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 firs...