Vaccination history and recency shape humoral responses to seasonal influenza vaccination: the SHIVERS-II cohort in New Zealand, 2018

Antibody responses to seasonal influenza vaccination are shaped by immune history, but the effects of prior vaccination frequency and recency on standard serological endpoints remain incompletely defined. We analyzed paired pre- and post-vaccination hemagglutination inhibition and neuraminidase inhibition titers from 775 adults in the New Zealand SHIVERS-II cohort during the 2018 influenza season and related these to vaccination histories (2013–2017). Post-vaccination titers increased across groups, but participants vaccinated more frequently were less likely to meet conventional ≥4-fold rise and seroconversion criteria, particularly for A/H3N2. Notably, these lower probabilities occurred despite higher absolute post-vaccination titers among frequently vaccinated participants. Longer intervals since the most recent vaccination were associated with higher probabilities of meeting these thresholds; neuraminidase responses showed similar patterns. Pre-vaccination titers were strongly correlated with post-vaccination titers and inversely associated with fold-rise magnitude. These findings indicate that vaccination frequency and recency shape measured humoral responses and highlight that fold-rise-based immunogenicity metrics should be interpreted in the context of baseline immunity and immune history. Despite lower fold rise responses in some groups, most participants showed measurable increases in HAI and NAI titers following vaccination, consistent with ongoing immunologic recall; these serologic findings should not be interpreted as evidence of reduced clinical protection, which was not assessed in this study.