IgA is necessary and sufficient to prevent norovirus infection in mice.

Authors

Arya B Ökten, Renata B Filler, Justin L Kung, Zhenhao Fang, Brieyanna C McWilliams, Jenna E Muscat-Rivera, Michael S Kegel, Ilze M Olivi Gomes, Madeleine C Mankowski, Ashwin N Skelly, Jilian R Melamed, Timothy J Nice, Sanghyun Lee, Megan T Baldridge, Thomas J Smith, Christiane E Wobus, Stephanie C Eisenbarth, Adam Williams, Leonid A Serebryannyy, Daniel C Douek, Drew Weissman, Sidi Chen, Edward F Kreider, Joseph E Craft, Craig B Wilen

Published in

Science translational medicine. Volume 18. Issue 855. Pages eaeb4878. Jun 24, 2026. Epub Jun 24, 2026.

Abstract

Human norovirus is the leading cause of viral gastroenteritis, yet effective vaccines and therapeutics remain elusive. Using murine norovirus as a model, we found that mucosal immunoglobulin A (IgA) is both necessary and sufficient for protection against infection, whereas CD8⁺ T cells are dispensable. Robust intestinal IgA production requires at least 4 weeks of enteric infection, consistent with kinetics of human norovirus RNA clearance. Systemic vaccination elicits high titers of neutralizing serum IgG but fails to prevent enteric norovirus infection, phenocopying a recent human norovirus vaccine failure. In contrast, prophylactic delivery of dimeric anti-norovirus IgA via mRNA lipid nanoparticles confers sterilizing immunity. Together, these findings define a critical role for mucosal IgA in norovirus protection and identify IgA-based treatments as a therapeutic approach for human norovirus.

PMID:
42341085
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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