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J Virol. 2016 May 12;90(11):5315-5328. doi: 10.1128/JVI.00230-16. Print 2016 Jun 1.

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

Author information

1
Université Paris Sud, INSERM, CEA, DRF-Department of Immunology of Viral Infections and Autoimmune Diseases (IMVA), UMR1184, IDMIT Infrastructure, iMETI, Fontenay-aux-Roses, France.
2
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
3
Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
4
Department of Medicine and CFAR, University of Alabama at Birmingham, Birmingham, Alabama, USA.
5
INSERM U1219, INRIA SISTM, University of Bordeaux, Bordeaux, France.
6
Vaccine Research Institute, Creteil, France.
7
Novartis Vaccines, Cambridge, Massachusetts, USA.
8
Mucosal Infection and Immunity Group, Department of Medicine, St. Mary's Campus, Imperial College London, London, United Kingdom.
9
Mucosal Infection and Immunity Group, Department of Medicine, St. Mary's Campus, Imperial College London, London, United Kingdom r.shattock@imperial.ac.uk.

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.

PMID:
27009957
PMCID:
PMC4934744
DOI:
10.1128/JVI.00230-16
[Indexed for MEDLINE]
Free PMC Article

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