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Differential cross-reactivity to the influenza B virus haemagglutinin underpins lineage-specific susceptibility between birth cohorts

Edler, P.; Schwab, L. S. U.; Aban, M.; Wille, M.; Spirason, N.; Deng, Y.-M.; Carlock, M. A.; Ross, T.; Juno, J. A.; Rockman, S.; Wheatley, A. K.; Kent, S. J.; Barr, I.; Price, D. J.; Koutsakos, M.

2023-08-28 immunology
10.1101/2023.08.25.554879 bioRxiv
Show abstract

Influenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that engender differential cross-reactivity to future influenza viruses, but direct serological evidence linked to susceptibility is limited. We analysed hemagglutination-inhibition titres in 1451 cross-sectional samples collected between 1992-2020, from individuals born between 1917-2008, against influenza B virus (IBV) isolates from 1940-2021, including future isolates that circulated after sample collection. We demonstrate that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the two IBV antigenic lineages, explaining lineage-specific age distributions of observed medically attended IBV infections. Our data bridge a critical gap between early life exposure, cross-reactivity, and influenza epidemiology and identify a plausible model to further dissect the interplay between host immunity, viral evolution and epidemiology.

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