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

Abstract

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.

A Perspective on the Structural and Functional Constraints for Immune Evasion: Insights from Influenza Virus

“…Overall, these observations highlight the importance of “original antigenic sin” in protection against zoonotic influenza viruses. They also reaffirm that seasonal influenza virus infection or vaccination can elicit heterosubtypic antibodies against antigenically similar zoonotic influenza viruses [108, 146–149]. …”

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting

“…Our findings raise questions about whether seasonal influenza vaccination might boost broadly-protective anti-HA responses (27) or alter imprinting from natural infection in IAV-naïve children. By exposing IAV-naïve children simultaneously to group 1 (H1N1) and group 2 (H3N2) antigens, vaccination might confer dual imprinting to both HA groups, or prevent strong imprinting against either HA group—or it could have no effect beyond delaying the age of imprinting via the first natural infection.…”

“…In particular, primary exposure to H5N1 or H7N9 can activate HA stem-specific reactivities induced by previous infection by H1 or H3, respectively (12,13,26). Indeed, others have suggested that heterosubtypic antibodies might attenuate disease from other IAV strains and may be imprinted to some degree by childhood exposure, though their serological assays provided no ability to detect or predict actual patterns of protection relevant to H5N1 and H7N9 in human populations (27). …”

The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals

“…It is suspected that some influenza vaccines, such as the H1/pdm09 vaccine, promote production of cross-reactive antibodies, whereas original antigenic sin (OAS), that is the preferential expansion of memory B cell clones from the initial immune response [2][3][4], most likely restricts their generation. We could recently show that repetitive vaccination of HIVnegative individuals generally stimulates homo and heterosubtypic responses [5].…”