Abstract
Abstract It is known that early exposures with influenza viruses impact the outcome of subsequent encounters. However, how sequential exposures to antigenically variant viruses shape the humoral immune response remains very poorly understood. To address this, a longitudinal analysis of antibody titers against pandemic (Japan/57 H2N2, Hong Kong/68 H3N2 and USSR/77 H1N1) and seasonal (Alabama/81 H3N2 and Texas/91 H1N1) strains of influenza virus was performed on matched serological samples collected over a 20 year period (1987-2008). These samples were obtained from the Framingham Heart Study Offspring Cohort. Sustained increases in neutralizing antibody titers were observed against both the pandemic and seasonal isolates. Hemagglutinin stalk-reactive antibody titers rose modestly over the 20 year study period, even in the absence of major antigenic shifts which are known to boost these antibodies most effectively. Neutralizing antibody titers against cytomegalovirus were also investigated. In contrast to influenza virus, no sustained increase in neutralizing antibody titers specific to cytomegalovirus was observed. These findings represent the first detailed longitudinal analysis of the humoral immune response against influenza virus in humans, and suggest a unique role for sequential exposures to antigenic variants in the maintenance of neutralizing antibodies.
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