March 21, 2023

Developing an effective norovirus vaccine would be an enormous win for global health — but researchers face a major challenge in the sheer diversity of the virus. Human noroviruses are divided into more than 35 genotypes, making it impossible to find one “silver bullet” vaccine.

However, in a hopeful new study led by virologists in the Baric Lab at the UNC-Chapel Hill Gillings School of Global Public Health, researchers homed in on the fact that variants within the GII.4 genotype currently cause 50% to 70% of all norovirus outbreaks in the world, driven by emergent virus variants.

Norovirus is the leading global cause of acute gastroenteritis, which brings on a combination of nausea, vomiting, diarrhea and abdominal pain. Children under five years old and the elderly are most affected by this virus, which causes more than 200,000 deaths each year.

In search of a possible solution, the researchers explored GII.4-related “immune imprinting,” which is the tendency of the human immune system to quickly misidentify a new virus variant as an older virus variant it has already encountered — as if seeing a doppelganger — and respond with antibodies for the old variant that are less effective at stopping the new virus. This process can hinder the body’s ability to block infection with new variants.

Norovirus immune imprinting is likely established in childhood when people first encounter the virus. The researchers wanted to learn if  exposure to GII.4 variants in the past may alter the effectiveness of children’s  immune response to currently circulating variants.

Lisa Lindesmith

Lisa Lindesmith

“Understanding these differences is the key for creating effective vaccines for both young children and seniors, who we would expect to have had different variant exposures in their childhoods,” says Research Program Manager Lisa Lindesmith, MS, a senior scientist  with the Gillings School’s Department of Epidemiology. “To better understand how humans develop antibody mediated immunity to norovirus GII.4 variants, we examined neutralizing antibody responses in about 700 young children.”

The researchers analyzed how blood samples from participants responded to a panel of GII.4 variants responsible for four different norovirus pandemics that occurred in 2002, 2006, 2009 and 2012.

The team was able to chart the development of population-level immunity to a newly emergent GII.4 variant. They mapped the corresponding remodeling of antibody responses, essentially observing in real time as the children’s immune systems updated their strategy for countering viral infection.

“This study demonstrates why children may be reinfected with similar virus variants,” Lindesmith says.” (The team members also identified a signature of immune imprinting in the modified antibody responses.) “We believe that if a pediatric norovirus vaccine is given early enough — say, around six months old — to prevent most first symptomatic infections, the vaccine may guide the antibody response in children as natural infection does in the absence of vaccination. Unfortunately, contact with a single variant does not provide durable protection from infection with new variants.”

Ultimately, the study indicates that for a norovirus vaccine to be effective against emergent variants, vaccine strategies will need to provide breadth of protective antibody responses early in life. Using information gleamed from these findings, researchers in the Baric Lab will continue their work on vaccines designed to protect children from norovirus infection throughout their life span.

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