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

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...

Full description

Bibliographic Details
Main Authors: Jessica M. van Loben Sels, Kim Y. Green
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/5/432
_version_ 1818288358265192448
author Jessica M. van Loben Sels
Kim Y. Green
author_facet Jessica M. van Loben Sels
Kim Y. Green
author_sort Jessica M. van Loben Sels
collection DOAJ
description 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.
first_indexed 2024-12-13T01:55:07Z
format Article
id doaj.art-371240e009604999a3cea560b47fb8b8
institution Directory Open Access Journal
issn 1999-4915
language English
last_indexed 2024-12-13T01:55:07Z
publishDate 2019-05-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj.art-371240e009604999a3cea560b47fb8b82022-12-22T00:03:25ZengMDPI AGViruses1999-49152019-05-0111543210.3390/v11050432v11050432The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and TherapeuticsJessica M. van Loben Sels0Kim Y. Green1Caliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USACaliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USAHuman 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.https://www.mdpi.com/1999-4915/11/5/432norovirusadaptive immunitymonoclonal antibodiesepitope mappingT cell epitopesB cell epitopestherapeutic antibodiesnanobodies (VHH)scFvuniversal vaccines
spellingShingle Jessica M. van Loben Sels
Kim Y. Green
The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
Viruses
norovirus
adaptive immunity
monoclonal antibodies
epitope mapping
T cell epitopes
B cell epitopes
therapeutic antibodies
nanobodies (VHH)
scFv
universal vaccines
title The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
title_full The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
title_fullStr The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
title_full_unstemmed The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
title_short The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics
title_sort antigenic topology of norovirus as defined by b and t cell epitope mapping implications for universal vaccines and therapeutics
topic norovirus
adaptive immunity
monoclonal antibodies
epitope mapping
T cell epitopes
B cell epitopes
therapeutic antibodies
nanobodies (VHH)
scFv
universal vaccines
url https://www.mdpi.com/1999-4915/11/5/432
work_keys_str_mv AT jessicamvanlobensels theantigenictopologyofnorovirusasdefinedbybandtcellepitopemappingimplicationsforuniversalvaccinesandtherapeutics
AT kimygreen theantigenictopologyofnorovirusasdefinedbybandtcellepitopemappingimplicationsforuniversalvaccinesandtherapeutics
AT jessicamvanlobensels antigenictopologyofnorovirusasdefinedbybandtcellepitopemappingimplicationsforuniversalvaccinesandtherapeutics
AT kimygreen antigenictopologyofnorovirusasdefinedbybandtcellepitopemappingimplicationsforuniversalvaccinesandtherapeutics