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

Arya B &#xd6;kten; 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

doi:10.1126/scitranslmed.aeb4878

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

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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.

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Animals Norovirus Caliciviridae Infections Immunoglobulin A Mice Humans CD8-Positive T-Lymphocytes Mice, Inbred C57BL Antibodies, Viral Immunoglobulin G Journal Article

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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. 2026-06-24. IgA is necessary and sufficient to prevent norovirus infection in mice.. https://doi.org/10.1126/scitranslmed.aeb4878

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