Assessment of timing for influenza vaccination among older adults in Japan: the Vaccine Effectiveness, Networking,...

In Japan, seasonal influenza vaccination is recommended for older adults between October and mid-December; however, the optimal vaccination timing remains unclear owing to waning immunity and variable epidemic patterns. In this study, we aimed to assess the effectiveness of different vaccination strategies in reducing influenza-related outcomes in older adults.

Using data from the vaccine effectiveness, networking, and universal safety study, we conducted a target trial emulation including adults aged ≥65 years across four influenza seasons (2016/2017, 2017/2018, 2018/2019, and 2019/2020). We applied a cloning, censoring, and weighting approach. Each individual was cloned and assigned to one of seven vaccination strategies at the start of October: no vaccination, vaccination during October, October-November, October-December, November, November-December, or December. Outcomes included influenza, influenza-related hospitalization, and all-cause mortality. Risk ratios (RRs) and risk differences, relative to no vaccination, were estimated at the end of March for each season based on standardized cumulative incidence.

Annual cohorts included 131 178-138 438 individuals (meanage: 76-77 years; male sex: 40.7-41.0%). The influenza incidences and RRs varied by season. Delayed vaccination was associated with the lowest influenza incidence in the 2017/2018 and 2018/2019, but not in the other seasons. Influenza-related hospitalizations showed seasonal trends similar to those of influenza. In contrast, early vaccination strategies generally led to reduced all-cause mortality across all seasons. The RRs were 0.80-0.93, 0.80-0.95, 0.82-1.00, and 0.81-0.96 in the 2016/2017, 2017/2018, 2018/2019, and 2019/2020 seasons, respectively. The risk differences were larger for mortality than for the influenza-related outcomes.

The effectiveness of each timing strategy varied depending on the outcome and season. Although delayed vaccination was associated with a lower influenza incidence in some seasons, early vaccination generally reduced all-cause mortality.