Pantaleo Poxvirus Vaccine Development Consortium
OVERVIEW:
The DNA prime/poxvirus boost (DNA/NYVAC) was developed in1998 by the EuroVacc program and since 2006 is the vaccine platform being further developed within the CAVD’s Poxvirus T cell Vaccine Discovery Consortium. The DNA/NYVAC platform has been tested in multiple phase I and II clinical trials in Europe and has shown to be highly immunogenic. The proposed project represents further development of the DNA/NYVAC platform targeted to improve both the magnitude of the T-cell response (particularly CD8 T cell response) and breadth of the response. The primary goal of the project is to investigate whether the 2nd generation DNA-C/NYVAC-C vaccine combination together with novel immunization strategies is able to increase response magnitude and breadth and induce balanced Env versus Gag, Pol and Nef HIV-1-specific T cell response in humans. In parallel the researchers are also investigating in the non-human primate model the efficacy of the 2nd generation DNA-C/NYVAC-C regimen against SIVmac251 challenge. The combined clinical and NHP challenge study data will provide the scientific basis for moving the DNA-C and NYVAC-C vaccine candidates to a phase IIB trial in Africa.
RESEARCH OBJECTIVES:
1. GMP manufacturing of the 2nd generation DNA and NYVAC vaccine candidates
2. Conduct toxicity studies as requested by the regulatory authorities
3. Conduct SIVmac251 challenge study in non-human primates
4. Conduct a phase I safety and immunogenicity study in Switzerland/US to generate the first safety data in humans with the 2nd generation DNA+NYVAC products
5. Conduct phase IIB clinical study in Sub-Saharan Africa
The proposed project offers a unique opportunity to explore in humans whether Env immunodominance can be overcome through different strategies including a) changes in HIV immunogens design, b) changes in vaccine formulation, i.e. different Env versus gag, pol-nef ratios, and c) spaced anatomic injection of the trivalent DNA and bivalent NYVAC vaccine candidates.