Key result
Characterization of GII.4 capsid protein epitopes defined by monoclonal antibody binding reveals the antigenic landscape of human norovirus, providing a road map for vaccine and therapeutic design.
Why the study?
Extensive antigenic diversity between genotypes and within the GII.4 genotype presents major challenges for the development of a broadly protective human norovirus vaccine.
This review maps the antigenic landscape of GII.4 human norovirus to guide future vaccine and therapeutic development.
Antigenic diversity hinders norovirus vaccine progress; leaves open broadly protective strategies for vulnerable groups.
Human norovirus is the leading cause of viral acute onset gastroenteritis disease burden, with 685 million infections reported annually. Vulnerable populations, such as children under the age of 5 years, the immunocompromised, and the elderly show a need for inducible immunity, as symptomatic dehydration and malnutrition can be lethal. Extensive antigenic diversity between genotypes and within the GII.4 genotype present major challenges for the development of a broadly protective vaccine. Efforts have been devoted to characterizing antibody-binding interactions with dynamic human norovirus viral-like particles, which recognize distinct antigenic sites on the capsid. Neutralizing antibody functions recognizing these sites have been validated in both surrogate (ligand blockade of binding) and in vitro virus propagation systems. In this review, we focus on GII.4 capsid protein epitopes as defined by monoclonal antibody binding. As additional antibody epitopes are defined, antigenic sites emerge on the human norovirus capsid, revealing the antigenic landscape of GII.4 viruses. These data may provide a road map for the design of candidate vaccine immunogens that induce cross-protective immunity and the development of therapeutic antibodies and drugs.
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Mallory et al. (2019) conducted a review in Human norovirus. Characterization of GII.4 capsid protein epitopes defined by monoclonal antibody binding reveals the antigenic landscape of human norovirus, providing a road map for vaccine and therapeutic design.