Grant: Fellowship - PA: HIV/AIDS CHVI Vaccine Discovery and Social Research

Prevention of HIV transmission requires approaches that interrupt the early phase of infection such as viral entry. This step of the viral cycle is mediated by the viral envelope glycoproteins (Env) which interact consecutively with the receptor CD4 and the coreceptors, CXCR4 or CCR5 The HIV-1 Env trimer formed on the virion surface represent the only virus-specific antigen recognized by the immune system and therefore, constitutes the sole target for neutralizing antibodies targeting HIV-1. The inability to induce antibodies (Abs) capable of neutralizing a broad spectrum of HIV-1 isolate of various clades, called broadly neutralizing Abs (bNAbs), has been a major obstacle for vaccine development. Recent advances in the field enabled identification of a plethora of novel bNAbs providing valuable new reagents and opportunities for HIV vaccine design. In order to interrupt the early phase of viral infection, we propose an original approach to identify bNAbs specifically targeting the conformation that Env samples before receptor engagement, which could lead to the identification of a new class of potent bNAbs. By specifically targeting the unbound conformation of HIV-1 Env, the breath and potency of these Abs might be enhanced. This proposal, by identifying a new class of potent bNAbs targeting HIV Env before receptor engagement, might be critical for the design of an efficient HIV-1 vaccine. Additionally, depending on the potency of the isolated bNAbs, some could be used therapeutically. Finally, our proposal represents a major Canadian initiative, since for the first time, bNAbs against HIV would be identified in Canada.