Measures of population immunity can predict the dominant clade of influenza A (H3N2) and reveal age-associated differences in susceptibility and specificity

Abstract

AbstractFor antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared to others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross-sectional antibody-derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season. We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains. The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titers to different HA and NA clades varied dramatically between individuals but showed significant associations with age, suggesting dependence on correlated past exposures. Despite this correlation, inter-individual variability in antibody titers to H3N2 strains increased gradually with age. This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza.Author summaryThe rapid evolution of influenza requires semi-annual updates to the strains included in influenza vaccines. New vaccine strains are frequently chosen based on their ability to escape immunity to other strains, with the degree of escape estimated from experimental infections of ferrets. However, the cross-reactivity derived from ferret experiments does not always match measures in people, who often have a long history of influenza exposures. We conducted a large cross-sectional serological study involving 483 individuals between 1 and 90 years of age and tested their sera against the major surface protein of eight circulating influenza strains. Levels of neutralizing antibody successfully predicted the dominant strain in the next influenza season. Different age groups showed different patterns of binding, although there was substantial variability in responses within age groups and an increase in the diversity of neutralizing antibody profiles with age. Our study demonstrates the feasibility of using cross-sectional sera to estimate major selection pressure on influenza.