Effect of the time of day for vaccination on the immune response to Ebola Virus Disease vaccines: A modeling study from PREVAC randomized trial

BACKGROUND: Emerging evidence suggests that the time in the day of vaccination may influence post-vaccination immunogenicity. The main objective of this study was to assess the association between the time of vaccination and the anti-EBOV GP1,2 IgG antibody response at 12 mo following vaccination against Ebola virus disease (EVD). METHODOLOGY/PRINCIPAL FINDINGS: This study utilized data from a randomized, double-blind, placebo-controlled international phase 2b clinical trial (PREVAC) evaluating the immunogenicity of three vaccination strategies against Ebola virus disease (rVSVΔG-ZEBOV-GP one and two doses, and Ad26.ZEBOV/MVA-BN-Filo) in 1,859 healthy Western Africans. In the overall population, we measured a statistically significant association between the time of day of first vaccination and anti-Ebola virus immunoglobulin G levels at 12 mo (p = 0.02). The magnitude of this association was small, participants vaccinated at 1600 h were estimated to have 1-7% lower antibody levels at 12 mo compared to those vaccinated at 1000 h. CONCLUSIONS/SIGNIFICANCE: An effect of the time of first vaccination on the antibody responses was found but remains modest and unlikely to impact the EVD vaccine effectiveness. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov registration: NCT02876328.