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A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus
Nadine C Salisch1, Kathryn E Stephenson2, Kristi Williams3
1Janssen Vaccines and Prevention, Leiden, the Netherlands (N.C.S., F.C., L.V., M.N.H., R.C.Z., J.H., C.P.C., M.L., M.D., J.V., H.S.).
Insights
A novel Zika virus (ZIKV) vaccine, Ad26.ZIKV.001, demonstrated strong safety and immunogenicity in healthy adults. The vaccine candidate induced robust neutralizing antibody titers and T-cell responses, offering promise for future ZIKV prevention.
Area of Science:
- Virology and immunology
- Vaccine development and clinical trials
- Infectious disease prevention
Background:
- Zika virus (ZIKV) poses a significant threat, particularly concerning severe congenital diseases transmitted from mother to fetus.
- Currently, no effective vaccine is available to prevent ZIKV infection.
Purpose of the Study:
- To evaluate the safety and immunogenicity of Ad26.ZIKV.001, a candidate prophylactic vaccine against ZIKV.
- To assess different dosing regimens and their impact on immune responses.
Main Methods:
- A Phase 1, randomized, double-blind, placebo-controlled study involving 100 healthy adult volunteers.
- Participants received Ad26.ZIKV.001 (adenovirus serotype 26 vector encoding ZIKV M-Env) in 1- or 2-dose regimens or a placebo.
- Safety assessments included local and systemic adverse events. Immunogenicity was measured by neutralization titers (MN50) and T-cell responses. Exploratory studies assessed antibody-mediated protection in a mouse model.
Main Results:
- Ad26.ZIKV.001 was well-tolerated across all tested regimens, with no identified safety concerns.
- Two-dose regimens induced high ZIKV neutralizing antibody titers that persisted for at least one year.
- A single dose of 1x10^11 viral particles (vp) achieved seroconversion in all participants, with sustained titers for over a year. Env-specific cellular responses were also observed.
Conclusions:
- Ad26.ZIKV.001 exhibits a favorable safety and immunogenicity profile in healthy adults.
- The vaccine candidate shows promise for further development as a prophylactic measure against ZIKV, particularly if the need for such a vaccine reemerges.
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.
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