Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast?
Open accessAbstract
The rapid development of multiple vaccines providing strong protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major achievement. There is now compelling evidence for the role of neutralizing antibodies in protective immunity. T cells may play a role in resolution of primary SARS-CoV-2 infection, and there is a widely expressed view that T cell-mediated immunity also plays an important role in vaccine-mediated protection. Here we discuss the role of vaccine-induced T cells in two distinct stages of infection: firstly, in protection from acquisition of symptomatic SARS-CoV-2 infection following exposure; secondly, if infection does occur, the potential for T cells to reduce the risk of developing severe COVID-19. We describe several lines of evidence that argue against a direct impact of vaccine-induced memory T cells in preventing symptomatic SARS-CoV-2 infection. However, the contribution of T cell immunity in reducing the severity of infection, particularly in infection with SARS-CoV-2 variants, remains to be determined. A detailed understanding of the role of T cells in COVID-19 is critical for next-generation vaccine design and development. Here we discuss the challenges in determining a causal relationship between vaccine-induced T cell immunity and protection from COVID-19 and propose an approach to gather the necessary evidence to clarify any role for vaccine-induced T cell memory in protection from severe COVID-19.
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Multivalent influenza and cytomegalovirus mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines.
“Multivalent influenza21 and cytomegalovirus22 mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines18,23.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [23]
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SARS-CoV-2 antibody response in persons with past natural infection
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SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques
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T cell-oriented strategies for controlling the COVID-19 pandemic
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Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults
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Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain
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Self-citationA meta-analysis of Early Results to predict Vaccine efficacy against OmicronPreprint
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Self-citationCutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses
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Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
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Flagged first, then by citations
Research works printed but not linked: 4
- [36]Cele S Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization Nature 2021 602 654 656 10.1038/s41586-021-04387-1 35016196 PMC8866126 · DOI · Paper page
- [58]Koutsakos M Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection medRxiv 2021 10.1101/2021.12.23.21268285 · DOI
- [59]Kared H Immunity in Omicron SARS-CoV-2 breakthrough COVID-19 in vaccinated adults medRxiv 2022 10.1101/2022.01.13.22269213 PMC9293966 35851055 · DOI
- [90]Stadler E Determinants of passive antibody effectiveness in SARS-CoV-2 infection medRxiv 2022 10.1101/2022.03.21.22272672 · DOI
Cited by
Sorted by citations
Neutralising antibodies predict protection from severe COVID-19
Cromer, D., Steain, M., Reynaldi, A., Schlub, T. E., Sasson, S. C., Kent, S. J., Khoury, D. S., & Davenport, M. P. (2022) · doi:10.1101/2022.06.09.22275942 · Cited by 139 · see citing works
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- Authors
- Kent, S. J., Khoury, D. S., Reynaldi, A., Juno, J. A., Wheatley, A. K., Stadler, E., John Wherry, E., Triccas, J., Sasson, S. C., Cromer, D., & Davenport, M. P.
- Affiliations
- The University of Melbourne (AU)
- UNSW Sydney (AU)
- The University of Sydney (AU)
- Corresponding author
- Kent, Stephen J.
- Davenport, Miles P.
- ORCID
- Venue
- Nature Reviews Immunology
- Published
- 2022-04-28
- Volume
- 22
- Issue
- 6
- Pages
- 387-397
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC9047577
- OpenAlex
- W4225011156
- Cited by
- 139
- References
- 97
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 26 · 2023: 52 · 2022: 31
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion)
- Funders
- National Institutes of Health (AI082630, AI149680, AI108545)
- National Health and Medical Research Council (1149990, 2007221)
- National Institute of Allergy and Infectious Diseases (R01AI105343, U19AI149680, R01AI155577, U19AI082630, P01AI108545)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- T cell immunity, COVID-19 pandemic, SARS-CoV-2, memory T cells, neutralizing antibodies, vaccine protection, disease severity, SARS-CoV-2 variants, causal inference, vaccine design
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Humans, Antibodies, Neutralizing
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