Profound CD8 T cell responses towards the SARS-CoV-2 ORF1ab in COVID-19 patients
Authors: Gangaev A. et al.
Link to paper: https://www.researchsquare.com/article/rs-33197/v1
Journal/ Pre-Print: Research Square
1. CD8 T cell reactivity towards SARS-CoV-2 is common in COVID19 patients
2. 2 novel HLA-A*01:01 restricted epitopes from Orf1ab, TTD and PTD, defined, and confirmed importance of A2-restricted YLQ epitope
3. 3/9 epitopes identified yielded shared responses
In this paper, the authors investigated the SARS-Cov2 specific CD8 T cell responses in 22 severe/critical or recovered COVID-19 patients. Most of the SARS-Cov2 specific CD8 T cell responses were found in recovering (from severe disease) and severe patients (not critical). They are mostly reactive (and in a higher magnitude) toward ORF1ab protein and not the S protein which is the main target for vaccine design studies at the moment. Further CD8 T cell characterization showed that SARS-Cov2 specific CD8 T cells express higher levels of NKG2A than bulk CD8 T cells which needs further investigation.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19: screen for epitope recognition in CD8 T cell response
Support for inclusion of a wider range of antigens (other than the S protein) in new vaccines to include a greater proportion of the CD8 response.
· Clinical Cohort study (very small cohort for immune characterization)
Strengths and limitations of the paper
Novelty: Not only focused on S protein which is the current target for vaccine design. Used a tatramer-based approach to show that non-spike proteins (in particular ORF1ab) include epitopes that drive CD8 T cell responses in this cohort. Even if it is still unclear whether a strong CD8 T cell response have a protective role.
Standing in the field: Lower number of epitope and HLA coverage compared to other studies but used a tetramer approach. https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3
Appropriate statistics: non-parametric statistical tests due to the very small sample size
Viral model used: hospitalized SARS-Cov2 infected patients
Translatability: Potentially diagnostic/prognostic
- Relatively few epitopes screened
- Low number of patients and controls
- No data concerning clinical conditions and viral load of patients.
- The tetramer positive cells could have been more intensively phenotyped.