Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates

Abstract

Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention.IMPORTANCE There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines.

Current prospects and future challenges for nasal vaccine delivery

“…There is a growing body of evidence to suggest that genetic material can be successfully delivered via this route, while recent studies have also demonstrated the advantages associated with combining the nasal with other routes of delivery or even combining vaccine with microbicide. 138 This review has focused primarily on prophylactic vaccines but there is encouraging evidence that nasal delivery will have a role to play in the design of therapeutic vaccines for e.g. cancers Alzheimer and autoimmune diseases.…”

Pharmaceutical Approaches to HIV Treatment and Prevention

“…In both experiments, the combination of vaccine and microbicide provided the best outcome . In another NHP study, the combination of a partially effective dose of 1% tenofovir vaginal gel with an intranasally and intramuscularly administered Env‐based vaccine was tested against 12 consecutive low‐dose SHIV‐SF162P3 vaginal challenges . The vaccine alone provided no protection, and even resulted in a greater infection rate than the control group.…”

“…The total risk reduction over the 24 exposures for this group was 91%. These studies showed that combining a microbicide with a vaccine provides increased levels of protection compared to either alone …”

“…Mucosal vaccines are also being investigated further to potentially provide greater protection at the portals of entry. Additionally, combining vaccines with microbicides has been shown to increase protection more than by solely the sum of their efficacies in NHP studies . This is an area that will continue to be explored to achieve greater prevention.…”

Séance bi-académique de l’Académie nationale de médecine et de l’Académie des Sciences: « Confiance et défiance vis-à-vis des vaccins »

“…Pasteur) et/ou de peau humaine [23] (comme la Plateforme de B Combadière au CIMI) permettent de tester l'efficacité protectrice des réponses immunes induites par le vaccin. Plus proches de l'homme mais plus couteux les primates non humains permettent d'analyser finement l'efficacité de candidats vaccins anti-VIH, chikungunya, dengue dans la Plateforme IDMIT [25], très innovante, du CEA, ou anti-Ébola, comme dans le P4 de Lyon. D'autres modèles animaux permettent de tester des vaccins contre des zoonoses dans les plateformes françaises de haut niveau de l'INRA, de l'ANSES, École Vétérinaire.…”