Mentored Scientist Award

Developing functional human immunodeficiency virus (HIV) cure strategies remains a top priority in HIV research. In a recent combination immunotherapy trial (NCT04357821, the amfAR trial), two doses of broadly neutralizing antibodies (bNAbs), which represent a promising approach for the prevention and suppression of HIV infection, were applied for antrietrovirals (ARTs) treatment interruption (ATI). However, due to the need for high resolution of ATI and knowledge gap in tissue matrix, currently no bioanalytical tools were available to answer if residual bnAb in cells and tissue following washout of ARTs and bnAbs from plasma contributes to sustained antiviral or immune mediated “vaccinal” effects. To fill in this “blank”, this project proposed to develop bioanalytical methodologies for bnAbs detection during ATI. Specifically, an ELISA assay will be developed, for the first time, to quantify the bnAbs concentrations at tissue level. We will also determine the localization of bnAbs in gut matrix, together with novel in situ methods to detect distribution of viruses. This project could provide insights into the immunoactivities of bnAbs at the tissue level, which is crucial for understanding their efficacy in targeting the survival of viral reservoirs, viral control, tissue drug exposure, and elimination. Given the widespread investigation of bnAbs as therapeutics, the knowledge of quantification and distribution identification of bnAbs at the tissue level will lead to a clearer understanding of the interaction of bnAbs in tissue with virus and host immune responses.