The period of protection from repeat infection following symptomatic influenza is not well established due to limited availability of longitudinal data. Using data from a pediatric cohort in Managua, Nicaragua, we examine the effects of natural influenza virus infection on subsequent infection with the same influenza virus subtype/lineage across multiple seasons, totaling 2,170 RT-PCR-confirmed symptomatic influenza infections. Logistic regression models assessed whether infection in the prior influenza season protected against homologous reinfection. We sequenced viruses from 2011–2019 identifying dominant clades and measuring antigenic distances between hemagglutinin clades. We observe homotypic protection from repeat infection in children infected with influenza A/H1N1pdm (OR 0.12, CI 0.02–0.88), A/H3N2 (OR 0.41, CI 0.24–0.73), and B/Victoria (OR 0.00, CI 0.00–0.14), but not with B/Yamagata viruses (OR 0.60, CI 0.09–2.10). Overall, protection wanes as time or antigenic distance increases. Individuals infected with one subtype or lineage of influenza virus have significantly lower odds of homologous reinfection for the following one to two years; after two years this protection wanes. This protection is demonstrated across multiple seasons, subtypes, and lineages among children.
Here Wraith et al. report homotypic protection from repeated influenza infection in a prospective pediatric cohort in Nicaragua followed for 9 years. This protection is observed across multiple seasons, subtypes, and lineages and is consistent for older and younger children.