Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals
Katharina Daniel, Leon Ullrich, Denis Ruchnewitz, Matthijs Meijers, Nico Joël Halwe, Ursula Wild, Jan Eberhardt, Jacob Schön, Ricarda Stumpf, Maike Schlotz, Marie Wunsch, Luana Girao Lessa, Elsayed Mohammed Abdelwhab, Maryna Kuryshko, Christopher Dietrich, Andreas Pinger, Anna-Lena Schumacher, Maximilian Germer, Malena Rohde, Christian Kukat, Lutz Gieselmann, Henning Gruell, Donata Hoffmann, Martin Beer, Thomas Erren, Michael Lässig, Christoph Kreer, Florian Klein
Abstract
The transmission of influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of an H5N1 pandemic. Pre-existing immunity strongly impacts the course and severity of viral infections, making detailed knowledge of antibodies against the spilled-over strain crucial. Here, we assessed humoral immunity against H5N1 A/Texas/37/2024 in H5N1-naive individuals. We performed complementary binding and neutralization assays on 66 individuals 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 with selected H1N1 or H3N2 strains. By cloning and characterizing 136 memory B cell-derived monoclonal antibodies, we identified potent A/Texas/37/2024-neutralizing antibodies in five out of six individuals we investigated. These antibodies cross-neutralized H1, competed with antibodies targeting the hemagglutinin (HA) stem, and protected mice from lethal H5N1 challenge. Our findings demonstrate partial pre-existing humoral immunity to A/Texas/37/2024 in H5N1-naive individuals.