Virus World

In a major step forward in the development of a norovirus vaccine, researchers discover a neutralizing antibody that can bind to a highly conserved epitope. For those who have suffered through a norovirus infection, commonly referred to as the “stomach flu,” the need for an effective vaccine does not really need explaining. But efforts to develop a vaccine against human norovirus have been unsuccessful, in part due to the virus’s rapid evolution and large number of antigenically distinct genotypes. Now, a group from the University of North Carolina (UNC) at Chapel Hill have discovered an antibody that broadly inhibits multiple strains of pandemic norovirus, a major step forward in the development of an effective vaccine for the dreaded stomach virus. The work describes, for the first time, the structure of the binding interaction between norovirus and a human antibody that may work against many strains.

 

Although ∼60% of human norovirus outbreaks are caused by the GII.4 genotype, there are more than 30 known genotypes. These rapidly evolving RNA viruses elicit complex serological responses associated with previous exposure. In order to further understand the immune response to the infection, the team of researchers first established the GII.4 repertoire of antibodies present before and after vaccination and selected several for epitope and structural analysis. They found that the antibodies following vaccination are polarized and shaped by previous norovirus infection stating that the “antibody response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions.” They went on to biochemically define the epitopes recognized by the antibodies with blockade activity to historical strains. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic strain.