IgA is necessary and sufficient to prevent norovirus infection in mice
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.
Authors
- Jilian R. Melamed (ORCID: https://orcid.org/0000-0003-0364-9334)
- Joseph Craft (ORCID: https://orcid.org/0000-0002-1368-6756)
- Adam Williams (ORCID: https://orcid.org/0000-0002-5151-4103)
- Christiane E. Wobus (ORCID: https://orcid.org/0000-0001-5286-0924)
- Daniel C. Douek (ORCID: https://orcid.org/0000-0001-5575-8634)
- Ashwin N. Skelly (ORCID: https://orcid.org/0000-0002-1565-3376)
- Renata B. Filler (ORCID: https://orcid.org/0000-0001-8579-8418)
- Leonid Serebryannyy (ORCID: https://orcid.org/0000-0003-0213-1779)
- Timothy J. Nice (ORCID: https://orcid.org/0000-0002-4471-7666)
- Stephanie C. Eisenbarth (ORCID: https://orcid.org/0000-0002-1244-208X)
- Zhenhao Fang (ORCID: https://orcid.org/0000-0002-1246-3665)
- Drew Weissman (ORCID: https://orcid.org/0000-0002-1501-6510)
- Madeleine C. Mankowski (ORCID: https://orcid.org/0000-0002-8640-174X)
- Edward F. Kreider (ORCID: https://orcid.org/0000-0003-2330-8430)
- Sidi Chen (ORCID: https://orcid.org/0000-0002-3819-5005)
- Megan T. Baldridge (ORCID: https://orcid.org/0000-0002-7030-6131)
- Arya Ökten (ORCID: https://orcid.org/0000-0002-7460-7951)
- Craig B. Wilen (ORCID: https://orcid.org/0000-0003-2495-9403)
- Sanghyun Lee (ORCID: https://orcid.org/0000-0002-0736-1648)
- Thomas J. Smith (ORCID: https://orcid.org/0000-0002-0978-1494)
- Brieyanna C. McWilliams
- Ilze M. Olivi Gomes
- Justin L. Kung (ORCID: https://orcid.org/0009-0002-6033-2659)
- Michael S. Kegel (ORCID: https://orcid.org/0009-0006-4155-9881)
- Jenna E. Muscat-Rivera
Institutions
- Northwestern University (US)
- National Institutes of Health (US)
- Oregon Health & Science University (US)
- Washington University in St. Louis (US)
- Brown University (US)
- University of Michigan (US)
- Yale University (US)
- National Institute of Allergy and Infectious Diseases (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2026-06-24
- DOI
- https://doi.org/10.1126/scitranslmed.aeb4878
- Primary Topic
- Viral gastroenteritis research and epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Burroughs Wellcome Fund
- Cancer Research Institute
- National Institutes of Health