LB-18 - Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation

Background: Understanding the diversity, breadth, magnitude, and functional profile of the T cell response against SARS-CoV-2 in recovered COVID-19 individuals is critical to evaluate the contribution of T cells to produce a potentially protective immune response.

Methods: We used a multiplexed peptide-MHC tetramer approach to screen a total of 408 SARS-CoV-2 candidate peptide epitopes for CD8+ T cell recognition in a cohort of 30 individuals recovered from COVID-19. The peptides spanned the whole viral genome and were restricted to six prevalent HLA alleles; T cells were simultaneously characterized by a 28-marker phenotypic panel. The evolution of the SARS-CoV-2 T cell responses was then statistically modeled against time from diagnosis, and in relation to humoral and inflammatory response.Workflow for Study. A multiplexed peptide-MHC tetramer approach was used to screen SARS-CoV-2 candidate peptide epitopes in a cohort of 30 COVID-19 recovered patients across 6 prevalent HLA alleles, and T cells profiled with a 28-marker phenotypic panel.
Multiplex tetramer screen. One representative COVID-19 recovered patient and one healthy donor were screened for HLA- relevant SARS-CoV-2 epitopes, as well as epitopes for CMV, EBV, Influenza, Adenovirus and MART-1. Shown are the frequencies of tetramer-positive CD8 T cells from 2 technical replicates per subject.


Results: Almost all individuals screened showed a T cell response against SARS-CoV-2 (29/30): 132 SARS-CoV-2-specific CD8+ T cells hits were detected, corresponding to 52 unique reactive epitopes. Twelve of the 52 unique SARS-CoV-2-specific epitopes were recognized by more than 40% of the individuals screened, indicating high prevalence in the subjects. Importantly, these CD8+ T cell responses were directed against both structural and non-structural viral proteins, with the highest magnitude against nucleocapsid derived peptides, but without any antigen-driven bias in the phenotype of specific T cells. Overall, SARS-CoV-2 T cells showed specific states of differentiation (stem-cell memory and transitional memory), which differed from those of MART-1, influenza, CMV and EBV-specific T cells.UMAP visualization revealed a phenotypic profile of SARS-CoV-2-specific CD8 T cells in COVID-19 convalescent donors that is distinct from other viral specificities, such as influenza, CMV, EBV and Adenovirus.
SARS-CoV-2 epitope screening revealed CD8+ T cell responses directed against both structural and non-structural viral proteins, with the highest magnitude response against nucleocapsid derived peptides


Conclusion: The kinetics modeling demonstrates a dynamic, evolving immune response characterized by a time-dependent decrease in overall inflammation, increase in neutralizing antibody titer, and progressive differentiation of a broad SARS-CoV-2 CD8 T cell response. It could be desirable to aim at recapitulating the hallmarks of this robust CD8 T cell response in the design of protective COVID-19 vaccines.

Presenter and Author(s)

• MF

  Michael Fehlings, PhD

  Scientific Director
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)

  Slides

Co-Author(s)

• HK

  Hassen Kared, PhD

  Scientist
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)
• EB

  Evan Bloch, M.B.Ch.B., M.S

  Associate Professor of Pathology
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AR

  Andrew Redd, PhD

  Staff Scientist
  NIH
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AN

  Alessandra Nardin, DvM

  Chief Operating Officer
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)
• HS

  Hermi Sumatoh, BSc, Dip MTech

  Senior Research Officer
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)
• FK

  Faris Kairi, BSc

  Research Officer
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)
• DC

  Daniel Carbajo, PhD

  Bioinformatician
  ImmunoScape
  Singapore, Singapore

  Disclosure: ImmunoScape (Shareholder)
• BA

  Brian Abel, PhD, MBA

  Director of Technical Business Development
  immunoSCAPE
  SAN FRANCISCO, California

  Disclosure: ImmunoScape (Shareholder)
• EN

  Evan Newell, PhD

  Associate Professor
  Fred Hutch
  Seattle, Washington

  Disclosure: ImmunoScape (Shareholder)
• OL

  Oliver Laeyendecker, PhD, MBA

  Associate Professor
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TB

  Tania Bonny, PhD

  Postdoctoral Research Fellow
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• SB

  Sarah Benner, PhD

  Postdoctoral Research Fellow
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AP

  Andy Pekosz, PhD

  Professor
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AT

  Aaron Tobian, PhD, MD

  Professor of Pathology
  Johns Hopkins University
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TQ

  Thomas Quinn, MD, MSc

  Chief, International HIV/STD Section
  NIAID
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.