Human antibodies: from natural and artificial engineering to the analysis of repertoires
Final Report Abstract
An enormous diversity of antibodies protects us from various infectious diseases by binding and neutralizing pathogens. During my postdoctoral work, we discovered a new type of antibody that inserts a pathogen-receptor to gain reactivity to the malaria parasite Plasmodium. The project and my independence started in July 2018, by devising a dedicated method to study insert-antibodies. By now, my team has deciphered the prevalence and molecular characteristics of such events and showed that in any human donor, inserts from diverse genomic regions contribute diversity to the antibody repertoire. In the frame of this project, we laid the foundation for the exploration of the underlying mechanism and its exploitation for the engineering of B cells. Beyond, we developed independent lines of research including our SARS- CoV-2 related projects. We showed that autoantibodies in COVID-19 can be divided into target-specific and promiscuous reactivities, of which the latter are less likely to have a functional impact on pathogenesis. Furthermore, we deciphered a mechanism of immune suppression by virus host receptors. This project laid the foundation to develop a novel, structure-guided approach to design vaccines, which lack interactions with host receptors while maintaining immunogenicity. Consequently, my research profile is now clearly distinct from my former supervisors. In addition to the Emmy Noether fellowship, I won 2 grants, including the ERC starting grant. I am part of a Helmholtz COVID-19 consortium. We built an interactive and dedicated team that enjoys tackling relevant research questions and engaged in diverse collaborations. In the future, we strive for a universal marker of DNA-repair and the innovation of B cell engineering and vaccine design.
Publications
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Different classes of genomic inserts contribute to human antibody diversity. Proceedings of the National Academy of Sciences, 119(36).
Lebedin, Mikhail; Foglierini, Mathilde; Khorkova, Svetlana; Vázquez, García Clara; Ratswohl, Christoph; Davydov, Alexey N.; Turchaninova, Maria A.; Daubenberger, Claudia; Chudakov, Dmitriy M.; Lanzavecchia, Antonio & de la Rosa, Kathrin
