Pantaleo: Poxvirus-Based Vaccine Development
The primary goal of the Pantaleo-led research consortium is to generate highly attenuated replication-com- petent poxvirus vectors that would substantially improve the breadth of HIV-1-speciﬁc vaccine induced immune responses. This strategy is also combined with the deletions of certain poxvirus genes known to interfere with the induction of the immune response. These newly generated vectors in addition to improving the magnitude and the quality of the vaccine induced HIV-1-speciﬁc T cell response, may serve as potent priming strategies for envelope protein-based vaccines and thus for the induction of potent antibody responses.
Furthermore, Pantaleo/CHUV was awarded with a 2nd grant to develop DNA/NYVAC platform. The DNA/ NYVAC platform has been tested in multiple phase I and II clinical trials in Europe and has shown to be highly immunogenic. This part of the 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.
1. Development of poxvirus-based vaccine candidate(s) with at least a 10-fold increase in immunogenicity as measured by the frequency of vaccine induced T-cells compared to the current poxvirus vectors and of novel formulation/delivery strategies.
2. Conduct NHP studies as well as PhI safety and immunogenicity study with the 2nd generation DNA and NYVAC vaccine candidates, to generate data for the ph IIB study in Sub-Saharan Africa.
At present, the research consortium has:
1. Completed several NHP studies:
a. Demonstrated that the new NYVAC and DNA vaccines developed within PTVDC are highly immuno- genic both in terms of T-cell and B-cell responses
b. Evaluated and compared different vaccine combinations, inserts and regimens, which have provided pivotal data for the design of future clinical studies;
2. In collaboration with HVTN, a number of phase I/II trials have been completed evaluating the safety and immunogenicity of different vaccination regimens combining DNA, NYVAC and protein vaccines in US and Sub-Saharan Africa. The more recent effort has been focused on the evaluation of DNA and protein combination, and the results have demonstrated that the combination elicits robust antibody and T-cell responses. Comparative analysis with the ALVAC/protein combination has shown that the DNA/protein regimen induces potent V1V2 responses, greater than the ALVAC/protein regimen, These responses were shown to be immune correlates of reduced risk from HIV infection in the RV144 trial. The DNA/protein is now planned for a phase IIB efficacy trial in Africa supported by a European program.
3. In collaboration with Hynes and Felber’s group, an NHP SHIV challenges study has been initiated, evaluating the protective efficacy of different homologous prime-boost regimens combining NYVAC-KC, DNA-HIV-PT123, Sequential CH505 DNA gp145s co-administered with gp120 proteins (the EnvSeq-2 vaccine) /GLA/SE.