Abstract
Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.
Competing Interest Statement
The authors have declared no competing interest.
Funder Information Declared
NIH NIAID, Division of Microbiology and Infectious Diseases, P01-AI089618
NIH NIAID Division of AIDS, Center for HIV/AIDS Vaccine Immunology, U19-AI067854
Source:
Link: https://www.biorxiv.org/content/10.64898/2026.07.16.738984v1
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