Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Open accessAbstract
Two zoonotic coronaviruses (CoVs)-SARS-CoV and MERS-CoV-have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.
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Adoptive transfer of antigen-specific T cells protected immunodeficient mice against challenge with SARS-CoV and MERS-CoV.
“Studies showed that adoptive transfer of antigen-specific T cells protected immunodeficient mice from infection after challenge with the SARS-CoV-2-related coronaviruses SARS-CoV and MERS-CoV52.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [52]
CD4+ T cells can prevent symptomatic SARS-CoV infection in animal models.
“Indeed, CD4+ T cells can prevent symptomatic SARS-CoV infection in animal models (Zhao et al., 2016), and the rapid induction of antigen-specific CD4+ T cells after only a single vaccine dose may explain the disconnect between low neutralizing responses and vaccine-induced protective immunity following the first dose.”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Zhao et al., 2016
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- Authors
- Zhao, J., Zhao, J., Mangalam, A. K., Channappanavar, R., Fett, C., Meyerholz, D. K., Agnihothram, S., Baric, R. S., David, C. S., & Perlman, S.
- Affiliations
- University of Iowa (US)
- University of North Carolina at Chapel Hill (US)
- Mayo Clinic (US)
- Corresponding author
- Zhao, Jincun
- Perlman, Stanley
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 44
- Issue
- 6
- Pages
- 1379-1391
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4917442
- OpenAlex
- W2418601731
- Cited by
- 496
- References
- 40
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 39 · 2023: 57 · 2022: 78 · 2021: 107 · 2020: 139 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 4
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Recruitment Program of Global Experts
- National Institutes of Health (PO1AI060699, AI100625, AI060699)
- National Institute of Allergy and Infectious Diseases (R01AI091322, U19AI100625, P01AI060699)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV, MERS-CoV, pan-coronavirus vaccine, conserved epitopes, cross-protective immunity, interferon-gamma, CD8+ T cell responses, HLA-DR2, HLA-DR3, bat coronaviruses, zoonotic coronaviruses, respiratory viral infections
- MeSH terms
- Animals, Antigens, Viral, Cells, Cultured, Cross Reactions, Humans, Immunity, Immunologic Memory, Interferon-gamma, Mice, Inbred Strains, Respiratory System, Vaccination, Viral Vaccines, Virion, CD4-Positive T-Lymphocytes, Coronavirus Infections, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice
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