TY - JOUR
T1 - T cell immunity is key to the pandemic endgame
T2 - How to measure and monitor it
AU - Schwarz, Megan
AU - Mzoughi, Slim
AU - Lozano-Ojalvo, Daniel
AU - Tan, Anthony T.
AU - Bertoletti, Antonio
AU - Guccione, Ernesto
N1 - Funding Information:
Research reported in this publication was supported in part by ISMMS seed fund and Dean's office grant to EG and MS. The authors gratefully acknowledge use of the services and facilities of the Tisch Cancer Institute supported by the NCI Cancer Center Support Grant ( P30 CA196521 ), in particular the Hess sequencing core and the BiNGS (Bioinformatics for Next Generation Sequencing) shared facility. MS was supported by a NCI training grant ( T32CA078207 ). AB and ATT acknowledge support from the Singapore Ministry of Health's National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060), the Singapore Ministry of Health's National Medical Research Council MOH-000019 (MOH-StaR17Nov-0001) and National Research Foundation, Singapore ( NRF-CRP17-2017-06 ).
Publisher Copyright:
© 2022 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - As vaccine deployment improves the healthcare emergency status caused by the SARS-CoV-2 pandemic, we need reliable tools to evaluate the duration of protective immunity at a global scale. Seminal studies have demonstrated that while neutralizing antibodies can protect us from viral infection, T cell-mediated cellular immunity provides long-term protection from severe COVID-19, even in the case of emerging new variants of concern (VOC). Indeed, the emergence of VOCs, able to substantially escape antibodies generated by current vaccines, has made the analysis of correlates of humoral protection against infection obsolete. The focus should now shift towards immunological correlates of protection from disease based on quantification of cellular immunity. Despite this evidence, an assessment of T cell responses is still overlooked. This is largely due to technical challenges and lack of validated diagnostic tests. Here, we review the current state of the art of available tests to distinguish between SARS-CoV-2 antigen-specific Tcells and non-antigen specific T-cells. These assays range from the analysis of the T cell-receptor (TCR) diversity (i.e. Immunoseq and MHC tetramer staining) to the detection of functional T cell activation (i.e. ICS, AIM, Elispot, ELLA, dqTACT, etc.) either from purified Peripheral Blood Mononuclear Cells (PBMCs) or whole blood. We discuss advantages and disadvantages of each assay, proposing their ideal use for different scopes. Finally, we argue how it is paramount to deploy cheap, standardized, and scalable assays to measure T cell functionality to fill this critical diagnostic gap and manage these next years of the pandemic.
AB - As vaccine deployment improves the healthcare emergency status caused by the SARS-CoV-2 pandemic, we need reliable tools to evaluate the duration of protective immunity at a global scale. Seminal studies have demonstrated that while neutralizing antibodies can protect us from viral infection, T cell-mediated cellular immunity provides long-term protection from severe COVID-19, even in the case of emerging new variants of concern (VOC). Indeed, the emergence of VOCs, able to substantially escape antibodies generated by current vaccines, has made the analysis of correlates of humoral protection against infection obsolete. The focus should now shift towards immunological correlates of protection from disease based on quantification of cellular immunity. Despite this evidence, an assessment of T cell responses is still overlooked. This is largely due to technical challenges and lack of validated diagnostic tests. Here, we review the current state of the art of available tests to distinguish between SARS-CoV-2 antigen-specific Tcells and non-antigen specific T-cells. These assays range from the analysis of the T cell-receptor (TCR) diversity (i.e. Immunoseq and MHC tetramer staining) to the detection of functional T cell activation (i.e. ICS, AIM, Elispot, ELLA, dqTACT, etc.) either from purified Peripheral Blood Mononuclear Cells (PBMCs) or whole blood. We discuss advantages and disadvantages of each assay, proposing their ideal use for different scopes. Finally, we argue how it is paramount to deploy cheap, standardized, and scalable assays to measure T cell functionality to fill this critical diagnostic gap and manage these next years of the pandemic.
KW - Cellular immunity
KW - SARS-CoV-2
KW - T-cells
KW - qPCR
UR - http://www.scopus.com/inward/record.url?scp=85137023849&partnerID=8YFLogxK
U2 - 10.1016/j.crimmu.2022.08.004
DO - 10.1016/j.crimmu.2022.08.004
M3 - Review article
AN - SCOPUS:85137023849
SN - 2590-2555
VL - 3
SP - 215
EP - 221
JO - Current Research in Immunology
JF - Current Research in Immunology
ER -