Vectored ImmunoProphylaxis Protects Humanized Mice from Mucosal HIV Transmission

The vast majority of new HIV infections result from relatively inefficient transmission(1,2) of the virus across mucosal surfaces during sexual intercourse(3). A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections(4). This natural bottleneck to transmission has stimulated efforts to develop interventions aimed at blocking this step of the infection process(5). Despite the promise of this strategy, clinical trials of pre-exposure prophylaxis have had limited degrees of success in humans, due in part to lack of adherence to the recommended pre-exposure treatment regimens(6,7). In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza(8) and HPV(9). We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV using broadly neutralizing antibodies(10). Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse viral strains, despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain(11), suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans.