Download Title: Clinical research fellowship on therapeutic and preventative

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.