MICA: Ad4HIV, A Phase I Trial Investigating Ad4, MVA and Protein Immunisation Strategies to Maximise Protective Antibody Responses to HIV-1 Envelope

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The global health burden associated with HIV continues to grow with 35 million people estimated to be living with HIV in 2013 and 2.3 million new infections. In absence of a cure, an effective vaccine would be the most sustainable way to prevent new HIV infections. We propose to make the most of what we have learned from a series of previous vaccine trials to design and test an HIV vaccine strategy which we believe will trigger a better immune response than those observed so far and potentially lead to the identification of a successful vaccine and vaccine strategy.The proposal brings together the scientific, clinical, and technical expertise and a range of vaccine products that are designed around a common HIV virus found predominantly in Southern and East Africa, India and Nepal and which has caused the world's worst HIV epidemics and is responsible for around half of all infections. The study will be conducted in collaboration with an industrial partner, PaxVax, and the UK HIV Vaccines Consortium (UK HVC). PaxVax is a fully integrated vaccine company, whose founders set out to develop and commercialize an innovative vaccine technology in a socially responsible manner for global impact. The UK HVC is a Wellcome Trust funded programme whose mission is to generate a series of candidate vaccines containing similar HIV antigens, such that direct comparison can be achieved to understand most rapidly the most immunogenic strategy for immunization in man.The design of the Ad4HIV trial is based on an immunisation regimen similar to that used in the only HIV vaccine trial to demonstrate partial efficacy (RV144, which showed an initial 60% reduction in infection rapidly waning to 31% in Thailand) and which builds on an existing MRC DCS funded study (UK HVC Spoke 003) to which it will be comparable. The Ad4HIV study will explore both the safety and immunogenicity of a novel combination of HIV vaccine candidates and will formally explore the immunological impact of a shorter and simpler prime-boost strategy using vaccine candidates provided by the UK HVC and designed to induce sustainable levels of protection form HIV acquisition of more than 60%. It will also explore the effectiveness of different boosting strategies with the added advantage of simplifying the regimen seen as crucial to vaccine feasibility.A successful and safe HIV vaccine would have considerable benefits across the general populations and high risk groups. It could have the potential to prevent over 70 million infections over the course of 15 years. Should the trial identify promising vaccine constructs or strategies, the research would support the design of the next clinical studies and provide an opportunity to inform and support decisions and policy making in several areas of HIV prevention.