Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques
Mohammad Arif Rahman, Massimiliano Bissa, Isabela Silva de Castro, Sabrina Helmold Hait, James D. Stamos, Farzana Bhuyan, Ruth Hunegnaw, Sarkis Sarkis, Anna Gutowska, Melvin N. Doster, Ramona Moles, Tanya Hoang, Lisa M. Jenkins, Ettore Appella, David Venzon, Hyoyoung Choo‐Wosoba, Timothy Cardozo, Marc M. Baum, Daniel H. Appella, Marjorie Robert-Guroff, Genoveffa Franchini
Abstract
Abstract The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV) mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIV mac251 , 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.