STOP-EBOLA

The Ebola virus one of the most virulent human pathogens. It induces a generalized haemorrhagic fever with a mortality rate of 25%-90%. Glycoprotein (GP), the unique surface protein and essential for infection, triggers virus attachment to the target cell and viral DNA release into the cytoplasm. The overall objective of this project is to better characterize these viral mechanisms and to obtain neutralizing camelid antibodies targeting key stages of infection. To this end, we will focus our research on obtaining neutralizing antibodies (nanobodies or vHHs) from camelid immunization with the Ebola virus glycoprotein. Nanobodies devoid of light chain have high affinities for their antigens and are easily produced in E. coli. Because infection by Ebola virus is a two-step process, these nanobodies will be assembled in constructions having specificity against the GP in general, for entry into the cell endosome, and against his binding site endosomal fusion site in view to block the release from the endosome. These constructions of neutralizing nanobodies will be tested in vitro and be co-crystallized with the GP in order to improve the binding strength nanobody-GP. Finally, these nanobodies will be used by the partner at the Pasteur Institute to achieve neutralization tests in vitro and by the P4 lab partner in Lyon for mice in vivo tests.