Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection

Rudragouda Channappanavar; Craig Fett; Jincun Zhao; David K Meyerholz; Stanley Perlman

doi:10.1128/JVI.01505-14

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Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection

Journal article

Open access

Peer reviewed

Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection

Rudragouda Channappanavar, Craig Fett, Jincun Zhao, David K Meyerholz and Stanley Perlman

Journal of virology, Vol.88(19), pp.11034-11044

10/2014

DOI: 10.1128/JVI.01505-14

PMCID: PMC4178831

PMID: 25056892

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Abstract

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. 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.

SARS Virus - immunology

Severe Acute Respiratory Syndrome - virology

Dendritic Cells - immunology

Humans

Peptides - genetics

Severe Acute Respiratory Syndrome - immunology

Antigens, Viral - genetics

Epitopes, T-Lymphocyte - genetics

Peptides - administration & dosage

CD4-Positive T-Lymphocytes - immunology

Immunity, Cellular - drug effects

Female

Epitopes, T-Lymphocyte - immunology

CD4-Positive T-Lymphocytes - virology

Dendritic Cells - virology

Antibodies, Viral - biosynthesis

Immunity, Active

Gene Expression

Immunization

Peptides - immunology

Severe Acute Respiratory Syndrome - mortality

Antigens, Viral - chemistry

SARS Virus - pathogenicity

Antigens, Viral - immunology

Severe Acute Respiratory Syndrome - prevention & control

Animals

CD8-Positive T-Lymphocytes - virology

Survival Analysis

Immunity, Humoral - drug effects

Immunologic Memory

Mice

CD8-Positive T-Lymphocytes - immunology

Dendritic Cells - transplantation

Details

Title: Subtitle: Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection
Creators: Rudragouda Channappanavar - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Craig Fett - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Jincun Zhao - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, Iowa, USA
Stanley Perlman - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA Stanley-perlman@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of virology, Vol.88(19), pp.11034-11044
DOI: 10.1128/JVI.01505-14
PMID: 25056892
PMCID: PMC4178831
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: AI091322 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS AI060699 / NIAID NIH HHS
Language: English
Date published: 10/2014
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777477902771

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