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PMID: 19079577 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Immune mechanisms responsible for vaccination against and clearance of mucosal and lymphatic norovirus infection.

PLoS pathogens ·Vol. 4 ·No. 12 ·2008-12-00 ·Pages e1000236

Chachu KA, LoBue AD, Strong DW, Baric RS, Virgin HW

Abstract

Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.

MeSH Terms
Animals B-Lymphocytes/immunology CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Caliciviridae Infections/immunology Capsid Proteins/genetics,immunology Gastroenteritis/immunology Immunity, Cellular Immunity, Mucosal Interferon-gamma/immunology,metabolism Lymph Nodes/immunology,virology Mice Mice, Inbred C57BL Norovirus/immunology Perforin/immunology,metabolism Spleen/immunology Statistics, Nonparametric Vaccination Vaccines, Attenuated/immunology Vaccines, Subunit/immunology Viral Proteins/genetics,immunology Viral Vaccines/immunology
Chemicals
Capsid Proteins Vaccines, Attenuated Vaccines, Subunit Viral Proteins Viral Vaccines Perforin Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chachu Karen A
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
LoBue Anna D
Strong David W
Baric Ralph S
Virgin Herbert W
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Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000236
Published
2008-12-00
Epub
2008-00-12
Pages
e1000236
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC2587711
Subset
IM
Grants
NIAID NIH HHS · R01 AI05635-02 · United States
NIAID NIH HHS · R01 AI065982 · United States
NIAID NIH HHS · R01 AI054483 · United States
NIAID NIH HHS · 5F31 AI 56665 · United States
NIGMS NIH HHS · T32 GM007200 · United States
NIAID NIH HHS · F31 AI056665 · United States
NIGMS NIH HHS · 5T32 GM007200 · United States
NIAID NIH HHS · R01 AI056351 · United States
External Links
PubMed source DOI: 10.1371/journal.ppat.1000236 PMC Full Text View journal details
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