Adjuvanted influenza vaccination increases pre-existing H5N1 cross-reactive antibodies and overcomes immune imprinting patterns

Abstract Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity and outcome have been observed in the past and are currently reported among infected farm workers in the US. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies. In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population and assess the effect of pH1N1/AS03 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We were able to detect H5N1 cross-neutralizing antibodies using a VSV-based pseudovirus system that correlated well with antibodies inhibiting the spread of authentic H5N1 viruses. Additionally, we found that pH1N1/AS03 vaccination increases H5N1 cross-reactive antibodies significantly, while non-adjuvanted influenza vaccination only had a marginal effect. Furthermore, we could show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination, that were erased by pH1N1/AS03 vaccination.