Detection of low pre-existing humoral immunity against influenza virus H5N1 clade 2.3.4.4b in unexposed individuals
Daniel, K.; Ullrich, L.; Ruchnewitz, D.; Meijers, M.; Halwe, N. J.; Wild, U.; Eberhardt, J.; Stumpf, R.; Schlotz, M.; Wunsch, M.; Girao Lessa, L.; Dietrich, C.; Pinger, A.; Schumacher, A.-L.; Germer, M.; Rohde, M.; Kukat, C.; Gieselmann, L.; Gruell, H.; Hoffmann, D.; Beer, M.; Erren, T.; Lässig, M.; Kreer, C.; Klein, F.
Show abstract
The spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic. Given the impact of pre-existing immunity on the course and severity of viral infections, we comprehensively assessed the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1-naive individuals. To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates. We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. By cloning and evaluating 136 monoclonal antibodies from memory B cells, we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies cross-neutralize H1, compete with antibodies targeting the HA stem, and protect mice from lethal H5N1 challenge. Our findings demonstrate partial pre-existing humoral immunity to A/Texas/37/2024 in H5N1-naive individuals.
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