-
Medical and health sciences
- Applied immunology
With over 37 million people infected globally, HIV remains a persistent epidemic. While combined antiretroviral therapy (ART) has improved life expectancy and quality of life for those with HIV, a cure is still out of reach. The primary challenge is the presence of latent HIV reservoirs, which form quickly after infection. Although ART suppresses viral replication in these reservoirs, the virus rapidly rebounds when treatment is stopped. These reservoirs are located in "sanctuary sites" like lymph nodes and the gut, hidden from the immune system. Cytotoxic T cells (CTLs) are crucial in controlling these reservoirs. This project aims to develop nanobody-based immunotherapeutics, specifically bispecific T-cell engagers (BiTEs), to enhance CTL activity against HIV reservoirs. The novel use of Nanobodies (Nbs), camelid single-domain antibodies with advantages over conventional immunoglobulins, will be explored. We will generate high-affinity broadly neutralizing Env Nbs and test their efficacy in vitro and in vivo using humanized mouse models of HIV.