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Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection.
- Source :
-
Journal of virology [J Virol] 2014 Oct; Vol. 88 (19), pp. 11034-44. Date of Electronic Publication: 2014 Jul 23. - Publication Year :
- 2014
-
Abstract
- Unlabelled: Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection.<br />Importance: Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.<br /> (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Animals
Antigens, Viral chemistry
Antigens, Viral genetics
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
CD8-Positive T-Lymphocytes virology
Dendritic Cells immunology
Dendritic Cells transplantation
Dendritic Cells virology
Epitopes, T-Lymphocyte genetics
Epitopes, T-Lymphocyte immunology
Female
Gene Expression
Humans
Immunity, Active
Immunity, Cellular drug effects
Immunity, Humoral drug effects
Immunization
Mice
Peptides administration & dosage
Peptides genetics
Peptides immunology
Severe acute respiratory syndrome-related coronavirus pathogenicity
Severe Acute Respiratory Syndrome immunology
Severe Acute Respiratory Syndrome mortality
Severe Acute Respiratory Syndrome virology
Survival Analysis
Antibodies, Viral biosynthesis
Antigens, Viral immunology
CD8-Positive T-Lymphocytes immunology
Immunologic Memory
Severe acute respiratory syndrome-related coronavirus immunology
Severe Acute Respiratory Syndrome prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 88
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 25056892
- Full Text :
- https://doi.org/10.1128/JVI.01505-14