Effect of time-of-day vaccination on the antibody response to mRNA and protein COVID-19 vaccine in adults

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not quantified - described as 'higher' for morning vs afternoon in Moderna group

• Primary Outcome: Antibody responses to SARS-CoV-2 variants at day 28 post-vaccination

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: Not reported

Clinical Application

Highly feasible intervention requiring only scheduling modification Directly relevant to Australian immunisation programs; could inform TGA guidance and ATAGI recommendations for optimal vaccination timing Adults receiving COVID-19 booster vaccinations, particularly those receiving mRNA vaccines

Abstract

Time-of-day vaccination has been suggested as a feasible method to boost COVID-19 vaccine immunogenicity particularly in high-risk groups. However, several studies report inconsistent findings. We explored if time-of-day vaccination influences antibody responses to a fourth dose of mRNA (Moderna bivalent vaccine; mRNA-1273.214/mRNA-1273.222) or protein (Novavax; NVX-CoV-2373) COVID-19 vaccine as part of a randomised controlled trial (RCT) in Melbourne, Australia. Furthermore, we assessed if time-of-day vaccination effects differed by vaccine type or sex. At day 28 post-vaccination, antibody responses to all SARS-CoV-2 variants tested were higher for morning compared to afternoon vaccination in the Moderna group. Males in the Moderna group responded with higher antibodies to all SARS-CoV-2 variants tested after morning vaccination while responses in females were unaffected by time-of-day vaccination. Time-of-day vaccination had no effect on the response to Novavax, regardless of sex. Larger randomised trials are needed to confirm these findings to optimise vaccine timing strategies.