ABSTRACT
The >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster.
Subject(s)
COVID-19ABSTRACT
Significant efforts are being made worldwide to understand the immune response to SARS-CoV-2, responsible for the COVID-19 pandemic, including the role of pre-existing T cell immunity. Understanding the mechanisms that promote cross-recognition by T cells induced by seasonal coronaviruses will be critical for future predictions on the role of pre-existing immunity in protection against severe disease. We demonstrate that the SARS-CoV-2 nucleocapsid (N) protein induces an immunodominant response in HLA-B7+ COVID-19-recovered individuals that is also readily detectable in unexposed donors. This immunodominant response is driven by a single N-encoded epitope that displays a high degree of conservation with the homologous region in circulating coronaviruses. We show that T cell-mediated cross-reactivity can be detected towards the circulating OC43/HKU-1 coronaviruses, but not the 229E or NL63 coronaviruses, due to different peptide conformations. This cross-reactivity is driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3b loop in unexposed and COVID-19-recovered individuals. Together, our findings demonstrate the basis of pre-existing immunity to a conserved and highly immunogenic SARS-CoV-2 epitope driven by cross-reactive memory T cells, suggesting long-lived protective immunity.Funding: This work was supported by generous donations from the QIMR Berghofer COVID 19 appeal, and financial contributions from Monash University, Australian Nuclear Science and Technology Organisation (ANSTO, AISNE ECR grants), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), and the Medical Research Future Fund (MRFF). H.S. is supported by an Australian Government Research Training Program Scholarship, E.J.G. was supported by an NHMRC CJ Martin Fellowship (#1110429) and is supported by an Australian Research Council DECRA (DE210101479), K.R.S.is supported by an Australian Research Council DECRA (DE180100512), S.G. is supported by and NHMRC SRF (#1159272).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This study was performed according to the principles of the Declaration of Helsinki.Ethics approval to undertake the research was obtained from the QIMR Berghofer Medical Research Institute Human Research Ethics Committee and Monash University Human Research Ethics Committee.