Increasing evidence suggests that timing of vaccine administration affects immune responses, with some studies indicating that morning administration of the influenza vaccine elicits a stronger antibody response than afternoon vaccination in older adults. Existing trials focused on antibody responses, contrasting two time groups (morning versus afternoon), without assessing other immunological parameters, such as T-cell responses, which also play a crucial role in immunity to respiratory viruses and may contribute to the time-of-day dependent response to vaccination. Therefore, the Chrono-Vax trial aims to determine the effect of influenza vaccination timing on antibody and T-cell responses across a continuous time window from 09:00-17:00 to gain novel insights into an optimal administration time. Additionally, this study will investigate how chronotype influences the relationship between vaccination timing and vaccine-induced immune responses and examine the impact of vaccination timing on the incidence of influenza-like illness (ILI) and influenza infection up to six months post-vaccination. A total of 440 adults aged 60-85 years will be included in the trial and receive the seasonal influenza vaccine at a random time between 09:00 and 17:00. Blood samples will be collected at baseline and 28 days post-vaccination to determine vaccine-induced immune responses. ILI symptoms and influenza infection will be monitored by participants up to six months after vaccination using a diary and rapid diagnostic self-tests, respectively. As such, the Chrono-Vax trial aims to determine the optimal time of day for influenza vaccination, thereby contributing to more effective vaccination strategies and increased protection against severe disease in older adults.
Keywords: Immune responses; Influenza vaccination; Randomized controlled trial; Time of day.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.