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

## TL;DR

This study found that the time of day when an Ebola vaccine is administered may slightly affect antibody levels, but the impact on vaccine effectiveness is minimal.

## Contribution

The study provides novel evidence that the time of vaccination may influence long-term antibody responses to Ebola vaccines.

## Key findings

- Participants vaccinated at 1600 h had 1–7% lower antibody levels at 12 mo compared to those vaccinated at 1000 h.
- The association between vaccination time and antibody levels was statistically significant but modest in magnitude.

## Abstract

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).

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.

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.

ClinicalTrials.gov registration: NCT02876328.

Vaccines are one of the most effective ways to prevent severe infectious diseases, but many factors can influence how well they work. One question that has received little attention is whether the time of day when a vaccine is given affects the immune response. In our study, we explored this idea in the context of vaccines against Ebola virus disease (EVD). We analyzed data from a large international clinical trial carried out in Western Africa, where different EVD vaccines were tested. We compared people who received their first vaccine in the morning with those who were vaccinated later in the afternoon. We found that the timing of vaccination was linked to small differences in antibody levels one year later. Participants vaccinated in the afternoon had slightly lower levels of antibodies than those vaccinated in the morning. However, this difference was modest and unlikely to change how well the vaccines protect against EVD. Our results suggest that the time of day may have a minor effect on how the immune system responds to vaccines, but it does not reduce the overall effectiveness of EVD vaccines.