Abstract
Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.
Highlights
Human norovirus (HuNoV) is a major cause of acute gastroenteritis and has emerged as the leading cause of severe childhood diarrhea in populations vaccinated against rotavirus [1,2]
This review aims to summarize the collective data of norovirus epitope mapping studies in order to elucidate common features of strain-specific and cross-reactive antigenic sites
This review summarizes progress in these areas that are attributable to nearly three decades of epitope mapping studies
Summary
Human norovirus (HuNoV) is a major cause of acute gastroenteritis and has emerged as the leading cause of severe childhood diarrhea in populations vaccinated against rotavirus [1,2]. Norovirus disease is associated with a higher risk of life-threatening dehydration in the young and old, immunocompromised individuals, and those with limited access to health care [8,9,10,11]. The CDC estimates that the U.S population experiences 19–21 million norovirus illnesses each year, with an estimated 570 deaths in children [12,13]. HuNoV has been estimated to cause approximately 200,000 deaths each year in children under five years old [1]. The financial toll associated with HuNoV infections is estimated to be $2 billion per year in the USA and $60 billion globally [12,14]
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