Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells

Catherine Riou; Georgia Schäfer; Elsa du Bruyn; Rene T Goliath; Cari Stek; Huihui Mou; Deli Hung; Katalin A Wilkinson; Robert J Wilkinson

doi:10.1183/13993003.00285-2021

Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells

Eur Respir J. 2022 Jan 13;59(1):2100285. doi: 10.1183/13993003.00285-2021. Print 2022 Jan.

Authors

Catherine Riou^{1

2}, Georgia Schäfer^{3

4

5}, Elsa du Bruyn^{3

6}, Rene T Goliath³, Cari Stek^{3

6

7}, Huihui Mou⁸, Deli Hung⁹, Katalin A Wilkinson^{3

6

10}, Robert J Wilkinson^{3

6

7

10}

Affiliations

¹ Wellcome Centre for Infectious Disease Research in Africa and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa cr.riou@uct.ac.za.
² Division of Medical Virology, Dept of Pathology, University of Cape Town, Observatory, South Africa.
³ Wellcome Centre for Infectious Disease Research in Africa and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.
⁴ International Centre for Genetic Engineering and Biotechnology (ICGEB) Cape Town, Observatory, South Africa.
⁵ Division of Medical Biochemistry and Structural Biology, Dept of Integrative Biomedical Sciences, University of Cape Town, Observatory, South Africa.
⁶ Dept of Medicine, University of Cape Town, Observatory, South Africa.
⁷ Dept of Infectious Diseases, Imperial College London, London, UK.
⁸ Dept of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
⁹ Dept of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
¹⁰ The Francis Crick Institute, London, UK.

Abstract

Background: Rapid tests to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity.

Methods: Using a rapid whole blood assay requiring a minimal amount of blood, we measured qualitatively and quantitatively SARS-CoV-2-specific CD4 T-cell responses in 31 healthcare workers using flow cytometry.

Results: 100% of COVID-19 convalescent participants displayed a detectable SARS-CoV-2-specific CD4 T-cell response. SARS-CoV-2-responding cells were also detected in 40.9% of participants with no COVID-19-associated symptoms or who tested PCR-negative. Phenotypic assessment indicated that, in COVID-19 convalescent participants, SARS-CoV-2 CD4 responses displayed an early differentiated memory phenotype with limited capacity to produce interferon (IFN)-γ. Conversely, in participants with no reported symptoms, SARS-CoV-2 CD4 responses were enriched in late differentiated cells, coexpressing IFN-γ and tumour necrosis factor-α and also Granzyme B.

Conclusions: This proof-of-concept study presents a scalable alternative to peripheral blood mononuclear cell-based assays to enumerate and phenotype SARS-CoV-2-responding T-cells, thus representing a practical tool to monitor adaptive immunity due to natural infection or vaccine trials.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Leukocytes, Mononuclear
Phenotype
SARS-CoV-2*
T-Lymphocytes

Abstract

Publication types

MeSH terms

Grants and funding