Chrono-optimization of influenza vaccine administration: A systematic review and meta-analysis

BackgroundThere is growing evidence that the strength of vaccine responses depends on the time of day of vaccine administration. This systematic review provides an overview of the literature regarding the effect of the timing of influenza vaccination on the vaccine response. To estimate the extent of this effect, we conducted a meta-analysis of randomized controlled trials (RCTs) in which antigen-specific antibody titers were monitored following either morning or afternoon administration of the influenza vaccine. Methods and resultsA systematic literature search identified five relevant studies that reported antigen-specific titers against multiple influenza vaccine strains after both morning and afternoon vaccination. Four of the five studies reported higher antibody titers for at least one vaccine strain following morning vaccination. Two RCTs were included in the meta-analysis, each of which reported the response to three vaccine strains, resulting in a total of six responses. The meta-analysis revealed that morning vaccination elicited a stronger antibody response than afternoon vaccination, with a pooled standardized mean difference (SMD) of 0.24 (95% CI=0.01-0.47). The between-study heterogeneity (I2=66%) was mainly due to the significantly 01greater effect of morning vaccination among adults aged 65 years or older than among adults aged 60 years or younger (SMD=0.32, 95% CI=0.21-0.43 versus SMD=0.00, 95% CI=-0.16-0.16, respectively). ConclusionInfluenza vaccinations administered in the morning induced a stronger antibody response in adults aged 65 years or older, who represent a major target group for influenza vaccination programs. Therefore, chrono-optimization of influenza vaccination could offer a safe and simple strategy for enhancing vaccine effectiveness. The paucity of relevant studies suggests that accounting for the time of vaccine administration in future vaccination trials could provide valuable insights into the potential benefits of chrono-optimization strategies.