Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility

Abstract

Most humans are infected with influenza viruses by 3-4 years of age (1) and have high antibody titers against viral strains encountered early in life (2). Early childhood influenza exposures can leave lifelong ‘immunological imprints’ that affect how an individual responds to antigenically distinct viral strains later in life (3,4). H3N2 influenza viruses began circulating in humans in 1968 and have evolved substantially over the past 51 years (5). Therefore, an individual’s birth year largely predicts which specific type of H3N2 virus they first encountered in childhood. Here, we completed a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We found that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. Most importantly, we found that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.