Macaque studies of vaccine and microbicide combinations for preventing HIV-1 sexual transmission

Abstract

Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell–based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine–microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately.

Theaflavin-3,3′-Digallate and Lactic Acid Combinations Reduce Herpes Simplex Virus Infectivity

“…Therefore, the more mechanisms that can be utilized to reduce shed HSV titers provided both by the microbicide and the mucosal immune system, the greater the probability of reducing viral transmission. Work supporting this principle has been provided recently by a study using combinations of vaccines and microbicides to reduce HIV transmission in a macaque model (50). The vaccine reduced the HIV load but not the acquisition of the virus, whereas the microbicide reduced HIV acquisition somewhat but had little effect on viral loads.…”

A Polyvalent Clade B Virus-Like Particle HIV Vaccine Combined with Partially Protective Oral Preexposure Prophylaxis Prevents Simian–Human Immunodeficiency Virus Infection in Macaques and Primes for Virus-Amplified Immunity

“…In another study in which an Ad26/Ad5 vaccine was combined with maraviroc, a CCR5 inhibitor, a 67% efficacy was demonstrated. 27 In both of these studies, peak viremia was reduced in the CBP breakthrough animals.…”

“…27 The partial preventive efficacy of adenovirus-based candidate HIV vaccines combined with a fusion inhibitor T-1249 or the CCR-5 inhibitor maraviroc was demonstrated against SIV or SHIV 162p3 infection. 27 A limitation of these studies was the sample size and lack of human preventive efficacy data of the microbicides. Neither of these studies evaluated oral PrEP, the only FDA-indicated PrEP strategy for HIV-1 prevention.…”

Semen-mediated Enhancement of HIV Infection Markedly Impairs the Antiviral Efficacy of Microbicides

“…Several animal studies demonstrated that neutralising antibodies have been successfully used to protect monkeys and mice from intravenous infection by SIV or HIV, and thus have potential to be developed as microbicides [13,14,16,49,60,103,[147][148][149]. As observed for the polyanions and SPL7013, neutralising antibodies lose antiviral efficacy in the presence of semen as well.…”