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Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection
Open accessAbstract
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. 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.
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“anti-S T-cell responses to the related SARS- and MERS-CoVs contribute toward viral clearance in normal as well as aged mice infected with SARS- or MERS-CoV, respectively (43–45).”
From An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [45]
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“Memory T cells, particularly those residing at the upper airways might limit disease severity and shorten the duration of disease by rapidly eliminating infected cells and coordinating the production of antibodies [67]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [67]
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Metadata
- Authors
- Channappanavar, R., Fett, C., Zhao, J., Meyerholz, D. K., & Perlman, S.
- Affiliations
- University of Iowa (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2014-10
- Volume
- 88
- Issue
- 19
- Pages
- 11034-11044
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC4178831
- OpenAlex
- W2004583429
- Cited by
- 411
- References
- 53
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 14 · 2023: 39 · 2022: 51 · 2021: 117 · 2020: 142 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 3
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI060699)
- National Institute of Allergy and Infectious Diseases (AI091322, R01AI091322, AI060699, P01AI060699)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK054759)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SARS-CoV, memory CD8+ T cells, T cell immunity, immunodominant epitopes, spike protein, prime-boost vaccination, peptide-loaded dendritic cells, vaccinia virus vector, lung viral load, cytokine production, granzyme B
- MeSH terms
- Animals, Antibodies, Viral, Antigens, Viral, Dendritic Cells, Female, Humans, Immunity, Active, Immunity, Cellular, Immunization, Immunologic Memory, Peptides, CD4-Positive T-Lymphocytes, Gene Expression, Survival Analysis, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Immunity, Humoral
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