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

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By G.M.

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.


Competing Interest Statement

DR, MM, CK, FK, and ML are members of the non-profit Center for Predictive Analysis of Viral Evolution (Previr). LG, HG, CK and FK are inventors on patent applications on virus neutralizing antibodies filed by the University of Cologne and have received payments from the University of Cologne for licensed patents.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.22.634277v2

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