A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine.
Ann Intern Med
; 174(5): 585-594, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1248392
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Vaccines
/
Zika Virus Infection
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Country/Region as subject:
North America
Language:
English
Journal:
Ann Intern Med
Year:
2021
Document Type:
Article
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