Each year, norovirus causes approximately 20 million cases of gastroenteritis (with abdominal cramping, diarrhea, and vomiting) in the United States. On a global scale, about 18% of the 1.8 billion cases of diarrheal disease worldwide, in 2010, were due to human norovirus. Several vaccine candidates are in clinical trials, but their effectiveness remains unknown.

In an effort to develop a treatment for norovirus infections, a team of researchers sought to isolate and map the epitopes of norovirus-specific human monoclonal antibodies that cross-react with diverse strains. The researchers isolated a panel of human monoclonal antibodies from subjects with a history of acute gastroenteritis that are cross-reactive and which neutralize a broad range of norovirus variants in laboratory tests. The information gathered by the team at Vanderbilt University Medical Center (VUMC) and the Baylor College of Medicine in Houston, TX, will be useful to inform future vaccine development.

This work is published in Nature Communications in the paper, “Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses.”

“We were surprised to find naturally occurring antibodies that recognized so many different noroviruses,” said James Crowe Jr., MD, director of the Vanderbilt Vaccine Center and professor of pediatrics and pathology, microbiology, and immunology at VUMC.

“Previously, many experts thought that this would not be possible because of the extreme sequence diversity in the various groups and types of noroviruses in circulation,” Crowe said. “The human immune system continues to surprise us in its capacity to recognize diverse virus variants.”

The team of researchers isolated and characterized a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs, and IgGs reactive with human norovirus. They described a conserved, antigenic site on the norovirus that could be used to reformulate vaccine candidates so that they are broadly effective against circulating viral strains. More specifically, they noted three binding patterns and identified monoclonal antibodies that neutralize at least one GI or GII norovirus strain when using a histo-blood group antigen (HBGA) blocking assay.

“One of the fascinating aspects of this study was the unexpected finding of where the human antibody attacks the virus for neutralization,” said B.V. Venkataram Prasad, PhD, the Alvin Romansky chair in biochemistry.

These studies identified human mAbs of various isotypes with an unexpected degree of breadth and neutralization activity. The monoclonal antibodies also could be used to treat or prevent norovirus infection directly or as diagnostic reagents, they added.

“It is exciting to now have human monoclonal antibodies that neutralize many norovirus variants,” added Mary Estes, PhD, the Cullen chair and professor of virology at Baylor College of Medicine.