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Review
. 2023 Jun 22;12(7):862.
doi: 10.3390/pathogens12070862.

The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic

Linda Petrone  1 , Alessandro Sette  2   3 , Rory D de Vries  4 , Delia Goletti  1
Affiliations
Review

The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic

Linda Petrone et al. Pathogens. .

Abstract

Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to "classical" T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial.

Keywords: SARS-CoV-2; T-cell response; cellular immunity; humoral immunity; immunocompromised; interferon-γ release assay; vaccination.

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Conflict of interest statement

DG has received consulting fees from Eli Lilly, PDB Biotech, and Quidel; she has received payment or honoraria from Amgen, Almirall, Biogen, bioMérieux, Celgene, DiaSorin, Janssen Biotech, and QIAGEN; and she has participated in data safety monitoring boards or advisory boards for Celgene and Eli Lilly. LP has no conflicts of interest to report. AS has received grants from the Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health; he has received consulting fees from AstraZeneca, Avalia Immunotherapies, Flow Pharma, Fortress, Gerson Lehrman Group, Gilead, Gritstone bio, Guggenheim, MEDACorp, Merck, Moderna, NA Vaccine Institute, QIAGEN, Rivervest, Sanofi, and Turnstone; he has received reimbursement for travel expenses from AstraZeneca, Aviara, Harvard, HLA, Keystone Symposia, Massachusetts General Hospital, Moderna, Ohio State University, Oxford University, Periscope, University of Oporto, and WVC; and he has filed for patent protection for various aspects of T-cell epitope and vaccine design work. RdV has no conflicts of interest to report.

Figures

Figure 1
Figure 1
Durability of the memory response to SARS-CoV-2. The different components of the memory response to SARS-CoV-2 after natural immunity, mRNA vaccination, or hybrid immunity show different kinetics defining the durability of the response and, therefore, the protection against severe disease and breakthrough infections. The scales are not quantitative. The CD4 or CD8 memory response is intended to spike for the mRNA vaccination and to the entire virus for the infection. The B memory and neutralizing responses are intended to spike. The infection is represented by SARS-CoV-2. In the “mRNA vaccination” plot, the booster dose is considered at 8 months. In hybrid immunity, the vaccination is considered at 6 months. In both cases, the vaccination is represented by a syringe. Footnotes: mRNA: messenger ribonucleic acid; Ab: antibody. Created with Biorender.com.
Figure 2
Figure 2
Factors impacting the immune response to SARS-CoV-2. The development of the adaptive immune response to SARS-CoV-2 may depend on host factors or viral features. The immune “status” of an individual at any moment (i.e., primary immunodeficiency or immune-mediated disorders), the age, and/or immunomodulating drugs are well recognized host factors that may have an impact on the induction and durability of both B and T-cell response to SARS-CoV-2. Moreover, viral factors as the emergence of new viral variants of concern, with higher degree of immune escape and infectivity, as well as the level of exposure to SARS-CoV-2, may be associated with a lesser immune protection against sever COVID-19 and breakthrough infections. Footnotes: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2. Created with Biorender.com.
Figure 3
Figure 3
Principle causes of impairment of T- and B-cell immunity for responding to SARS-CoV2 infection. The immune host background (i.e., inborn errors of immunity), infections, and several drugs may differently modify SARS-CoV-2-specific response. Known causes of T-cell response impairment are combined (SCID) as well as T-cell activation immunodeficiency syndromes, HIV infection, and drugs such as fingolimod or checkpoint inhibitors and anti-Pan T, used for immune-mediated disorders or malignancies. Similarly, B-cell response impairment may be attributed to SCID or antibody deficiencies and drugs that affect B-cell functions as anti-CD20. Footnotes: SCID: severe combined immunodeficiency; HIV: human immunodeficiency virus. Created with Biorender.com.
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