Immunity · 2026
Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals.
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Daniel Katharina, Ullrich Leon, Ruchnewitz Denis, Meijers Matthijs, Halwe Nico Joel, Wild Ursula, Eberhardt Jan, Schön Jacob, Stumpf Ricarda, Schlotz Maike, Wunsch Marie, Girao Lessa Luana, Abdelwhab Elsayed Mohammed, Kuryshko Maryna, Dietrich Christopher, Pinger Andreas, Schumacher Anna-Lena, Germer Maximilian, Rohde Malena, Kukat Christian, Gieselmann Lutz, Gruell Henning, Hoffmann Donata, Beer Martin, Erren Thomas, Lässig Michael, Kreer Christoph, Klein Florian
Аннотация
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.