Recherche Fondamentale (basic research) - Développement d'anticorps monoclonaux dirigés contre le domaine de fixation au récepteur (RBD) de cOVID-19 et caractérisation de leur réponse neutralisante à large spectre Generation of potent cross-neutralizing monoclonal antibodies against the receptor binding domain of COVID-19 virus

April 2020, the COVID-19 pandemic has causes more than 100 000 death worldwide. Therapeutics and development prophylactic vaccine are urgently and desperately needed. The aim of this project is to decipher the benefice of antibodies (Ab) directed against the receptor-binding domain (RBD) of COVID-19 as therapeutic or in vaccine strategies. This domain that directly interact with the host angiotensin-converting enzyme 2 (ACE2) receptor was previously proposed to be a relevant therapeutic and vaccine immunogen. Monoclonal Abs directed against the RDB of Middle East respiratory syndrome (MERS) coronavirus, responsible for the 2012 epidemic in Middle East, have shown interesting cross-neutralizing activities. However, these mAbs have only mild cross reactivity with the new coronavirus emerged in 2019, further suggesting that COVID-19 RBD display particular features. Moreover, as some potentially deleterious enhancing effects were described in vitro for certain RDB MERS-Cov specific antibodies, in depth characterization of the functional profile of the newly generated mAb is required. A strong collaboration between C. Moog's lab (U1109 INSERM) and F. Shokri's lab (Tehran University of Medical Sciences) will be developed to perform an in depth characterization of the functional activities of the Abs generated. As a second step, the potential efficacy of the most promizing mAbs generated will be tested in vivo using intranasally COVID-19 infected BALB/c mice transgenic for human ACE2 and CD147. The identification of RBD specific mAbs displaying functional cross-inhibitory activity against COVID-19 without deleterious toxic or enhancing effects will give clues for the use of such type of Abs for therapeutic intervention and will guide us for the development of vaccine immunogens.