Séminaire CIRI (21.12.2023) : Dr. Dimitri LAVILLETTE

Dr. Dimitri LAVILLETTE, Chief Scientific Officer; Applied Molecular Virology Laboratory; Institut Pasteur Korea; Gyeonggi-do, Republic of Korea, "Lessons from the Development of Neutralizing Human Monoclonal Antibodies and Camelidae single-domain antibodies Against SARS-CoV-2".

Abstract: To eradicate the global COVID-19 pandemic, scientists, doctors, and researchers took exceptionally diverse initiatives towards the development of new and effective diagnostics, vaccines and therapeutics to save many lives. The Spike glycoprotein (S) of SARS-CoV-2 is the primary determinant of viral tropism, and plays a vital role in cell receptor binding and membrane fusion.  Most neutralizing antibodies (nAbs) bind directly to the receptor binding domain (RBD), which results in direct blocking of virus–receptor interactions, while targeting conserved epitopes may lead to rare broadly neutralizing antibodies. 

RBD was chosen by us in early 2020 to screen several potential neutralizing antibodies through different technical approaches like convalescent patient B cell sorting, alpaca immunization, and in vitro synthetic single-domain antibodies (VHH). VHHs are the variable domains of heavy-chain antibodies (HCAb) found in Camelidae (~15 kDa) which have several potential advantages. All these approaches allowed us to isolate and to develop potent nAbs targeting both variable and conserved epitope as defined by cross neutralization experiments using variants and crystal structures. Their mode of actions was determined and their in vivo prophylactic potential evaluated. These analyses allowed us to gain knowledge and experience on these technologies, but it also helped us now to have a precise analysis of the pros and cons for the development of nAbs for the future pandemics.