Developmental Clinical Study - UK HVC 003 DMP Phase I Prime-Boost-ReBoost HIV vaccine trial

Lead Research Organisation: Imperial College London
Department Name: Research Office


The global health burden associated with HIV continues to grow with 33 million people estimated to be living with HIV in 2009 and 2.7 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 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 the UK HIV Vaccines Consortium (UK HVC) 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 UK HVC 001DMP trial is based on an immunisation regimen similar to that used in the only HIV vaccine trial to demonstrate partial efficacy (RV144, which showed a 31% reduction in HIV infection in Thailand). The study will explore both the safety and immunogenicity of this novel combination of HIV vaccine candidates and will formally explore the immunological impact of a prime, boost and re-boost strategy using different vaccine candidates provided by the UK HVC. It will also explore the effectiveness of combining vaccines candidate together with the added advantage of minimising the length of 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.

Technical Summary

A safe and effective preventive HIV vaccine remains one of the highest priorities for international public health. Despite slow progress, a recent phase III trial (RV144) demonstrated significant protection against HIV infection through a prime-boost strategy with a canary-pox viral vector (ALVAC), followed by an ENV (GP120) protein boost. The immune correlates of protection remain obscure, but consensus is that both antibodies to HIV and a strong cellular immune response are required. The UK HIV Vaccine Consortium (UK HVC) has developed a series of HIV immunogens with freedom to undertake clinical research, so that diverse combinations of viral vectors, DNA, protein and adjuvant can be directly compared to define the most immunogenic vaccine immunisation strategy. By building on our previous vaccine studies, we believe that the HVC 003 DMP immunisation strategies will be more immunogenic than the partially successful RV144. The UK HVC 003 DMP trial proposes to study two prime-boost strategies using GMP products. The priming will be done with DNA followed by modified pox (MVA) and boost with rGP140 protein adjuvanted with GLA. The study will compare 3X DNA followed by 2X MVA and 2X rGP140/GLA, versus 3X DNA, followed by concurrent MVA/rGP140/GLA, with a primary end-point of ENV antibody titre and secondary end-points of neutralisation and cellular immunity. If safe and highly immunogenic, we would wish to optimise the immunisation schedule through another comparative study and proceed with a phase II/III study in East and Southern Africa, as a university-based and led public-private partnership, based on the Microbicides Development Programme model.


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