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"... The findings ... upend traditional vaccine development efforts which to date have focused on creating norovirus-fighting antibodies that circulate in the blood rather than taking up residence in the gut.
According to findings, mucosal IgA (Immunoglobulin A) antibodies — which are found primarily in the body’s mucosal surfaces, including the lungs, airway, the intestines, and gut — provide key immune defense against norovirus. ...
“By using mouse models, we discovered that IgA was both necessary and sufficient for protection against norovirus.” ..."
From the editor's summary and abstract:
"Editor’s summary
Although most individuals recover from norovirus infection after an unpleasant few days, some individuals, such as infants, older adults, and immunocompromised individuals, are at risk of developing severe gastroenteritis. As such, vaccines to combat this infection are urgently needed. Here, Ökten et al. investigated which components of the immune system are required to effectively clear norovirus in a murine model. The authors found that intestinal IgA in particular was both necessary and sufficient for clearance of norovirus in mice.
To highlight the translational potential of these findings, the authors showed that delivery of an mRNA encoding an anti-norovirus dimeric IgA was able to protect mice.
Together, these results highlight the requirement for a successful norovirus vaccine to specifically elicit mucosal IgA and suggest that anti-norovirus IgA antibodies may offer a prophylactic or therapeutic option for at-risk populations. ...
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."
IgA is necessary and sufficient to prevent norovirus infection in mice (no public access)
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