Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection

PLoS Pathogens

Anna D. LoBue¹  Ralph S. Baric¹  Karen A. Chachu²  David W. Strong²  Herbert W. Virgin² 

[1] Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Vaccination;    immunization;    T cells;    Ileum;    Major histocompatibility complex;    Norovirus;    Cytotoxic T cells;    Calicivirus infection;    Gastrointestinal tract;   

DOI  :  10.1371/journal.ppat.1000236

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY