Hugo Mouquet

Our lab aims at studying the molecular basis of antibody B-cell responses to viruses such as HIV-1 and Hepatitis viruses, and how anti-viral antibodies may participate in controlling the infection in humans.

“Humoral memory” is composed of high affinity antibodies that mediate long-lived immunity against infectious agents, e.g., by providing protection against re-infection.

The molecular dissection of anti-pathogen B-cell responses using modern technologies to generate and characterize antigen-specific human monoclonal antibodies (mAbs) has allowed breakthrough discoveries on the humoral responses against pathogens such as HIV-1, Influenza, Ebola and Zika viruses.

These recombinant mAbs represent unique “fingerprints” for each B-cell clone and when characterized at a molecular and functional level, provide crucial information about the humoral response to the pathogen.

Moreover, in addition to the Ab’ therapeutic interest, it has now become evident that studying the biology of neutralizing mAbs is pivotal in designing candidate immunogens for vaccine development. In this context, our research focuses on understanding the mechanisms governing human Ab B-cell response to pathogens, and to make use of these findings to develop therapeutic strategies.

Using cutting-edge technologies including single-cell capture and cloning of human monoclonals, we are currently investigating the memory B-cell responses to HIV-1 at the peripheral and mucosal level in individuals who developed extremely potent and broad neutralizing HIV-1 antibodies (bNAbs), this in trying to understand how these rare antibodies develop. To get insights on how these bNAbs work, we are also currently characterizing their various antiviral properties such as their inhibitory activity against the passage of the virus through epithelial cells in mucosal tissues, as well as their additional antiviral functions known as effector functions. We are also trying to dissect the molecular and structural mechanisms responsible for their broad neutralizing activity against divergent HIV-1 strains. We are also involved in different collaborative projects such as one aiming at characterizing the role of antiviral drugs in restoring efficient antibody responses at mucosal sites.

About half of our research investigations also use this research approach and methodological strategy to study B-cell memory and biology in physiological conditions, and B-cell antibody responses to other viral pathogens, particularly those responsible for emerging infections as for example Chikungunya virus. Our research work also extends to human infections mediated by Hepatitis viruses, with the characterization of the complex relationship between autoimmunity and HCV infection.