Detection of low pre-existing humoral immunity against influenza virus H5N1 clade 2.3.4.4b 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 M. Abdelwhab; Maryna Kuryshko; Christopher Dietrich; Andreas Pinger; Anna‐Lena Schumacher; Maximilian Germer; Malena Rohde; Christian Kukat; Lutz Gieselmann; Henning Gruell; Donata Hoffmann; Martin Beer; Erren Tc; Michael Lässig; Christoph Kreer; Florian Klein

doi:10.1016/j.immuni.2025.12.013

ImmunologyImmunityJan 30, 2026

Peer-reviewed journal article

Detection of low pre-existing humoral immunity against influenza virus H5N1 clade 2.3.4.4b in unexposed individuals

Katharina Daniel iD, Leon Ullrich iD, Denis Ruchnewitz iD, Matthijs Meijers iD, Nico Joël Halwe iD, Ursula Wild iD, Jan Eberhardt, Jacob Schön iD, Ricarda Stumpf, Maike Schlotz, Marie Wunsch iD, Luana Girao Lessa, Elsayed M. Abdelwhab iD, Maryna Kuryshko iD, Christopher Dietrich, Andreas Pinger, Anna‐Lena Schumacher iD, Maximilian Germer iD, Malena Rohde, Christian Kukat iD, Lutz Gieselmann iD, Henning Gruell iD, Donata Hoffmann iD, Martin Beer iD, Erren Tc iD, , Florian Klein iD

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.

PDF DOI