PROJECT SUMMARY With the most people ever in history currently living with HIV, stopping the HIV epidemic remains imperative. Furthermore, preventing HIV infection in newborns via mother-to-child transmission (MTCT) continues to be a major objective in areas with limited resources for antenatal care. While antiretroviral treatment (ART) has been critical in reducing transmission of HIV-1, it is not without risk, including toxicity of ART drugs in newborns and the development of drug resistant viral variants. Thus, there is an urgent need for safer preventative measures to eliminate MTCT of HIV-1. We have demonstrated that the CCR5-specific antibody Leronlimab can be used as an effective pre-exposure prophylaxis (PrEP) regimen in macaques. Here, we are proposing to utilize AAV- vectored Leronlimab to facilitate in vivo delivery of Leronlimab expression in infant macaques to prevent perinatal SHIV infection. In specific aim 1, we will determine the ability of AAV9-delivered Leronlimab to prevent acquisition of SHIV in newborn macaques. In aim 2, we will characterize the long-term performance of AAV9 gene therapy administered to newborn macaques. This work would provide a safe and viable alternative to prevent vertical transmission of HIV-1 and support direct in vivo delivery of anti-HIV prophylactic modalities in infants.

PROJECT NARRATIVE Vertical transmission of HIV remains a major route of transmission in developing countries. Adeno-associated virus (AAV) vectors are a promising gene therapy delivery platform with the potential to provide an antibody treatment or prophylaxis with a single dose. Here we propose to give AAV-vector delivery of Leronlimab, a CCR5- blocking antibody, to infant macaques in order to prevent infection by SHIV.