Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

Background. The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive antibodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood. Methods. To determine the prevalence for human homo- and heterosubtypic antibody responses, we scrutinized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors. Results. It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic influenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination. Conclusions. We provide evidence that vaccinations stimulate both homo-and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains.