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The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

Caliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA
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Viruses 2019, 11(5), 432; https://doi.org/10.3390/v11050432
Received: 10 April 2019 / Revised: 7 May 2019 / Accepted: 8 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Noroviruses)
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. View Full-Text
Keywords: norovirus; adaptive immunity; monoclonal antibodies; epitope mapping; T cell epitopes; B cell epitopes; therapeutic antibodies; nanobodies (VHH); scFv; universal vaccines norovirus; adaptive immunity; monoclonal antibodies; epitope mapping; T cell epitopes; B cell epitopes; therapeutic antibodies; nanobodies (VHH); scFv; universal vaccines
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van Loben Sels, J.M.; Green, K.Y. The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics. Viruses 2019, 11, 432.

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