Title: Clinical research fellowship on therapeutic and preventative HIV vaccine
strategies. (PI Robin Shattock, CoPI Sarah Fidler)
Although antiretroviral treatment (ART) confers near-normal life expectancy for people living with HIV infection, this requires lifelong ART adherence, carrying the risk of drug-related toxicities, viral resistance and lifetime expense. Therefore, eradication of the virus has become the major research goal for the management of HIV infected individuals. Biological therapeutics utilizing vaccines in the context of ART and anti-latency drugs represents the most promising tools that could lead to ART- free survival. In order to confer ‘HIV Cure’ vaccination is given post infection, to enhance HIV-specific immunity effectively controlling viral replication. The primary goal of this project is to assess the role of vaccination in achieving sufficient viral control for prolonged ART free survival (ie "functional cure") following safety and immunogenicity studies in HIV-uninfected healthy controls.
The scientific objectives of the project are to:
 evaluate safety and immunogenicity of therapeutic vaccine strategies including the evaluation of HIV DNA-GTU® MultiHIV B clade vaccine designed by FIT Biotech – a fully funded vaccine study due to start Q2013
 develop a new therapeutic approach to the use of HIV vaccine for the elimination of HIV, in the context of wider treatment research across multiple BRC centers
 understand mode of administration for the development optimized vaccination strategies against HIV (inc electroporation, vector prime-boost) in infected and uninfected subjects
 understand the molecular basis of immune control of viral latency and the use of anti-latency drugs to expose reservoirs to immune eradication,
 To determine whether autologous vaccines based on individual patient viral sequences are more effective in eliminating HIV latency than heterologous standard HIV vaccine constructs.
 redirect immune responses toward cytotoxic T-cells trageted to eliminate viral latency.
The technological objectives of the project are to:
 develop optimized methods of DNA HIV vaccination in the context of ART
 advance existing standardization in immuno-monitoring
 advance existing standardization in monitoring of viral reservoirs and latency activation.
The training objectives of the project are to:
 develop DNA vaccination with electroporation for prophylactic and/or therapeutic application to with autologous and heterologous standard HIV vaccine constructs
 optimize methodology of ex-vivo culture to assess reactivation of viral latency
 to provide specific training in all aspects of translational vaccine research and the conduct phase I clinical trials.
The BRC objectives of the project are to:
 build on existing industry partnerships with FIT biotech, Novartis, Sanofi Pasteur and Gilead on vaccination and the use of anti-latency drugs
 To deliver patient-/ people- focused translational clinical research with patient studies
 To Develop/expand on the Public and Patient Involvement portfolio utilizing modern media tools: including the www.helpmakehistory.mrc.ac.uk
web site utilized for raising public awareness and subject recruitment
 Build on existing cross-BRC collaborative activity on the study of viral latency (Royal Free,
UCL, GKT, Oxford and Cambridge
 To leveraging of other grant funding by association with current strategic grant application to the Wellcome Trust to establish an experimental HIV vaccine research centre.