Cellular immunity against SARS-CoV-2
It is critical to develop a sound understanding of the T cell-mediated immune response against SARS-CoV-2. To this end, immunodominant T cell epitopes need to be identified. This information is also important for the future understanding of the quality of vaccine-induced responses.
Adaptive immune responses against infectious pathogens like SARS-CoV-2 include cellular immunity by CD4+ and CD8+ cells and virus-specific antibodies. While several recent studies have examined important aspects for host protection, numerous questions remain concerning: a) the immunodominant T cell epitopes, b) the extent of cross-reactivity with other viruses and vaccines including influenza, and c) whether the cellular immune response is also involved in organ complications, for example by cross-reactivity with self-tissues.
We aim to isolate T lymphocytes from individuals who have been infected with SARS-CoV-2 without any symptoms, and from individuals who have experienced acute or chronic organ damage, including from vaccines. We will characterise the target epitopes and compare the reactivity against these in individuals with a mild form of COVID-19, but also those with organ manifestations and after vaccination.
Expected results and envisaged products
With this project we identify important immunodominant T cell epitopes that can be used for characterising cellular immune responses and acquire knowledge about which T cells cross-react with other viruses, including vaccines. Furthermore, we expect to obtain information about those reactivities which indicate that the vaccine candidates induce robust cellular immunity against SARS-CoV-2. Finally, we can enhance our pathogenetic understanding as to whether the virus induces cross-reactivity against self-tissues and whether this is involved in severe organ manifestations during infection.
Specific contribution to tackle the current pandemic
An understanding of the natural course of SARS-CoV-2 infection, the mechanisms underlying protective immunity and the suspected pathogenic immune responses in certain COVID-related manifestations, is an important goal during the ongoing pandemic. Numerous vaccine candidates are being developed, and a sound understanding of the cellular immunity of the virus-induced and vaccine-related immunity is a prerequisite for choosing the best vaccines. Knowledge of the immunodominant T cell epitopes and the phenotype of virus-specific T cells is important.
Protective and Pathogenic T Cell Immunity During SARS-CoV-2 Infection