Year: 2026
Type: article
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.
Source: Science Translational Medicine
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
Institutions: Yale University, University of Pennsylvania, Oregon Health & Science University, Brown University, Washington University in St. Louis, The University of Texas Medical Branch at Galveston, University of Michigan, Northwestern University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: A multipronged, mRNA gene therapy approach to HIV cure, Viral immune evasion during intestinal norovirus infection, The role of tuft cells in norovirus pathogenesis, Role of norovirus capsid dynamics in adaptive immune evasion, G8510822112, G9000176434, G9000331242, Interdisciplinary Immunology Training Program
OpenAlex ID: W7165777267