Differential Kinetics of T Cell and Antibody Responses Delineate Dominant T Cell Epitopes in Long-Term Immunity after COVID-19

Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design. Funding: This work was supported by the Bundesministerium fur Bildung und Forschung (BMBF, FKZ:01KI20130; J.W.), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Grant WA 4608/1-2; J.W.), the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy (Grant EXC2180-390900677; S.S., H.-G.R., H.R.S., J.W.), the German Cancer Consortium (DKTK; S.S., H.-G.R., H.R.S.), the Wilhelm Sander Stiftung (Grant 2016.177.2; J.W.), the Jose Carreras Leukamie-Stiftung (Grant DJCLS 05 R/2017; J.W.) and the Fortune Program of the University of Tubingen (Fortune number 2451-0-0 and 2581-0-0; J.W.). Conflict of Interest: H.-G.R. is shareholder of Immatics Biotechnologies GmbH and Curevac AG. A.N., T.B., H.-G.R., and J.S.W. hold patents on peptides described in this manuscript secured under the numbers 20 169 047.6 and 20 190 070.1. The other authors declare no competing interests. Ethical Approval: The study was approved by and performed according to the guidelines of the local ethics committees (179/2020/BO2).