A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine.
Journal
Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
pubmed:
16
2
2021
medline:
7
8
2021
entrez:
15
2
2021
Statut:
ppublish
Résumé
Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available. To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate. Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561). United States. 100 healthy adult volunteers. Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 10 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. 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 The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population. The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges. Janssen Vaccines and Infectious Diseases.
Sections du résumé
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
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
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.
Substances chimiques
Viral Vaccines
0
Banques de données
ClinicalTrials.gov
['NCT03356561']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM