Post-exposure treatment with neutralizing monoclonal antibodies prevents SHIV infection in infant rhesus macaques and limits establishment of latent viral reservoirs (VAC11P.1102)

Abstract

Abstract We have developed a unique pre-clinical SHIV/macaque model with the potential to address translational implications of early intervention in mother-to-child-transmission (MTCT). Based on prior passive studies in this model, we hypothesized that very early therapeutic treatment with potent NmAbs would limit or ablate establishment of viral reservoirs in babies born to HIV-infected mothers. Fourteen one-month-old rhesus macaques were inoculated orally with SHIVSF162P3. Cocktails of NmAbs PGT121 and VRC07-523 were prepared for subcutaneous passive transfer. A control group of two animals did not receive NmAbs. Beginning at 24 hours (1 day) post SHIV exposure, NmAbs were delivered subcutaneously and repeated at days 4, 7, and 10. Blood samples monitored for plasma viral load (PVL) and transferred NmAb kinetics. Cell-associated viral loads (CAVL) were measured in PBMC and in tissues at necropsy. Animals were followed for 24 weeks to assess PVL, PBMC-based CAVL, and T and B cell responses. Controls were infected by three d.p.i. NmAb-treated infants had undetectable PVL with no evidence of CAVL in PBMC or tissue samples at necropsy. ICS was used to detect Gag and Vif T cell responses. No anti-SHIV T cell responses were detected in lymphocytes isolated from inguinal lymph nodes at week 20 or in necropsy tissue samples. Results indicate early therapeutic treatment with a cocktail of potent NmAbs can prevent infection and limit the establishment of latent viral reservoirs.