Long-term humoral immune responses against SARS-CoV-2 in healthy individuals and patients with primary immunodeficienciess

• Applicants: Professor Dr. Hermann Eibel; Professor Dr. Reinhard Voll; Professor Dr. Klaus Warnatz
• Subject Area: Immunology
• Term: Funded in 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458641632

SARS-CoV-2 infections can remain oligosymptomatic or end fatally despite of intensive care treatment. Therefore, the question whether one develops a lifelong protection against a second infection by SARS-CoV2 and which mechanisms contribute to the protection is highly relevant, especially also in the context of the current race for the best vaccine. So far, the development of SARS-CoV-2 specific memory B cells has not been studied in detail although memory B cells contribute essentially after convalescence or after vaccination against the coronavirus-induced disease (Covid-19) which develops in the course of SARS-CoV-2 infections. In this context, it is unclear which viral antigens are recognized by memory B cells, how long memory B cells can be detected and how the antigen specificity of memory B cells correlates with the specificity of serum antibodies and memory T cell responses directed against SARS-CoV-2. To approach these questions, we have established a cohort of more than 800 persons from the staff of the University Hospital Freiburg, of which - as we have been able show - about 10% have been exposed to SARS-CoV-2. In addition, in collaboration with other European centers we were able to create a small cohort of 10 patients with defined immunodeficiency syndromes, who have survived COVID19. In this cohorts we will analyze the subsets, specificity, frequency and longevity of SARS-CoV-2 reactive memory B cells over the time period of one year. In the cohort of immunodeficient patients we plan to investigate the formation and subset characteristics of virus-specific B- and T-cells in response to coronavirus infection as well as potential differences to immunocompetent donors. Once vaccinations against SARS-CoV-2 are available, we plan to carry out these studies with vaccinated individuals and compare the results with the data obtained from studying convalescents from SARS-CoV-2 infections. We hope that our approach will allow to determine the extent to which infections and vaccinations lead to a long-lasting B cell memory which can protect against Covid-19 resulting from re-infection with SARS-CoV-2., how this correlates with the development of a memory T cell response and to understand, which parameters correlate the best with a strong memory response.This approach will hopefully allow us to develop suitable strategies for vaccination against SARS-CoV-2 for PAD/CVID patients and survey their immune response over time.

• DFG Programme: Research Grants