Scientists at The University of Texas at Austin, in collaboration with researchers from the University of North Carolina at Chapel Hill and the National Institutes of Health, have discovered a strategy to fight back against norovirus, a leading cause of gastroenteritis worldwide. Their new study, published in Science Translational Medicine , identifies powerful antibodies capable of neutralizing a wide range of norovirus strains. The finding could lead to the design of broadly effective norovirus vaccine, as well as the development of new therapeutic antibodies for the treatment of norovirus-associated gastroenteritis.
Norovirus infects over 700 million people each year, causing severe diarrhea and vomiting. While most people recover, the virus poses a serious threat to young children, older adults and individuals with weakened immune systems. Developing a vaccine has been challenging because norovirus has many genetic variants and frequently mutates to evade herd immunity.
Using advanced molecular analysis, the research team studied the immune responses of participants who received an experimental oral norovirus vaccine developed by Vaxart. They discovered that some individuals produced broadly neutralizing antibodies that not only broadly neutralized multiple norovirus strains, including both historical and emerging variants, but also cross-neutralized multiple types of norovirus responsible for approximately 75% of global norovirus outbreaks.
"These findings provide critical insights into how the immune system responds to norovirus and pave the way for designing a vaccine that offers broad, long-lasting protection," said George Georgiou, co-corresponding author and professor of molecular biosciences and in the McKetta Department of Chemical Engineering at UT Austin. "We found antibodies that are very broad in terms of being able to neutralize many different variants that have circulated or are circulating now."
One of the most promising antibodies identified, VX22, targets a previously unknown weak spot in the virus's structure. Unlike typical antibodies that attack only one or two strains, VX22 neutralizes noroviruses from multiple genotypes by binding to a highly conserved region in the virus particles, making it a strong candidate for vaccine development.
"Norovirus cases this winter have surged to twice the two previous annual peaks, which really underscores the fact that norovirus is both prevalent and rapidly evolving, and we need a vaccine against it to reduce the global burden of diseases associated with norovirus," said Juyeon Park, first author and postdoctoral researcher at UT Austin. "Our findings can better inform the future design of vaccine development against norovirus."
Norovirus spreads easily through contaminated food, water and surfaces, often causing outbreaks in schools, cruise ships and healthcare facilities. A vaccine that protects against multiple strains could drastically reduce infections, hospitalizations and the economic burden of the disease.
The recently identified antibodies could also be used to develop a post-infection therapy that could be useful in treating immunocompromised people who cannot fight off the infection on their own, Georgiou said.
"This discovery brings us closer to a vaccine that could provide lasting protection and prevent the devastating effects of norovirus outbreaks, as well as potential treatment for those already infected," Georgiou said.
The research team is now working on refining the vaccine's design and testing the relevance of these findings in broader populations, such as among elderly people and young children.
Ed Satterwhite, Victoria Longo, Gregory C. Ippolito, Christina A. Martins, Jeffrey Marchioni, Yimin Huan and Jason J. Lavinder of UT Austin; Lisa C. Lindesmith, Paul D. Brewer-Jensen, Michael L. Mallory, Mark Zweigart, Samantha R. May, Yaoska Reyes and Ralph S. Baric of University of North Carolina Chapel Hill; Adam S. Olia, Ridhi Chaudhary and Peter D. Kwong of the Vaccine Research Center; Veronica P. Costantini and Jan Vinjé of the Centers for Disease Control; Cynthia E. Kelley and Joost Snijder of Utrecht University; Yaroslav Tsybovsky and Tyler Stephens of the Frederick National Laboratory for Cancer Research; and Becca Flitter and Sean N. Tucker of Vaxart were also authors on the paper.
The research was funded by the National Institute of Allergy and Infectious Disease at the National Institutes of Health, the Dutch Research Council, the Institute for Chemical Immunology, and the Vaccine Research Center at NIH. George Georgiou holds the Dula D. Cockrell Centennial Chair in Engineering.
Several of the authors have filed patent applications on some of the broadly neutralizing antibodies identified in this research.
