Tweet
Immunity
. 2026 Jan 30:S1074-7613(25)00569-2.
doi: 10.1016/j.immuni.2025.12.013. Online ahead of print.
Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals
Katharina Daniel 1 , Leon Ullrich 1 , Denis Ruchnewitz 2 , Matthijs Meijers 2 , Nico Joel Halwe 3 , Ursula Wild 4 , Jan Eberhardt 2 , Jacob Schön 3 , Ricarda Stumpf 1 , Maike Schlotz 1 , Marie Wunsch 5 , Luana Girao Lessa 1 , Elsayed Mohammed Abdelwhab 6 , Maryna Kuryshko 6 , Christopher Dietrich 4 , Andreas Pinger 4 , Anna-Lena Schumacher 7 , Maximilian Germer 7 , Malena Rohde 1 , Christian Kukat 7 , Lutz Gieselmann 5 , Henning Gruell 1 , Donata Hoffmann 3 , Martin Beer 3 , Thomas Erren 4 , Michael Lässig 2 , Christoph Kreer 8 , Florian Klein 9
Affiliations
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.
Keywords: A/Texas/37/2024; H5N1; clade 2.3.4.4b; cross-neutralizing antibodies; highly pathogenic avian influenza; humoral immunity; influenza virus; pre-existing antibodies.
. 2026 Jan 30:S1074-7613(25)00569-2.
doi: 10.1016/j.immuni.2025.12.013. Online ahead of print.
Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals
Katharina Daniel 1 , Leon Ullrich 1 , Denis Ruchnewitz 2 , Matthijs Meijers 2 , Nico Joel Halwe 3 , Ursula Wild 4 , Jan Eberhardt 2 , Jacob Schön 3 , Ricarda Stumpf 1 , Maike Schlotz 1 , Marie Wunsch 5 , Luana Girao Lessa 1 , Elsayed Mohammed Abdelwhab 6 , Maryna Kuryshko 6 , Christopher Dietrich 4 , Andreas Pinger 4 , Anna-Lena Schumacher 7 , Maximilian Germer 7 , Malena Rohde 1 , Christian Kukat 7 , Lutz Gieselmann 5 , Henning Gruell 1 , Donata Hoffmann 3 , Martin Beer 3 , Thomas Erren 4 , Michael Lässig 2 , Christoph Kreer 8 , Florian Klein 9
Affiliations
- PMID: 41619731
- DOI: 10.1016/j.immuni.2025.12.013
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.
Keywords: A/Texas/37/2024; H5N1; clade 2.3.4.4b; cross-neutralizing antibodies; highly pathogenic avian influenza; humoral immunity; influenza virus; pre-existing antibodies.