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Annual and Interim Progress Report Summaries

Principal Investigator: Giuseppe Pantaleo

 

Project: Poxvirus-Based Vaccine Development

Submitted April 1, 2012

Building on the EuroVacc program and the CAVD-PTVDC program, the PVRD 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. After the RV144 trial in Thailand testing a a poxvirus vector plus protein vaccination modality, which has provided for the first time evidence that an HIV vaccine can prevent infection, further adjustment are brought to the PVRD project.

In year 3, the manufacturing of the 2nd generation DNA and NYVAC have been completed and the GMP materials have been released. We have also completed a large immunogenicity and safety study in non human primates, comparing the immunogenicity of the highly attenuated replication competent NYVAC vs replication deficient NYVAC for its priming ability for protein boost with or without the combination with DNA. The data have demonstrated that: a) the new DNA and NYVAC have shown substantial improvement in the immunogenicity of the vaccine-induced T-cell responses, both CD4 and CD8 T-cell responses, with regard to magnitude, breadth and functional profile as compared to the 1st generation DNA and NYVAC vaccine, and b) substantial differences in the magnitude of T-cell and antibody responses in the immunization regimens with or without DNA prime. The findings in this study provided for the first time the in vivo data confirming the enhanced immunogenicity of the new DNA and NYVACs (both replication deficient and replication competent) developed under the CAVD program. This is also the first head-to-head comparison study between vaccination schedules with or without DNA priming and may provide further insights in the design of immunization regimens aiming at the induction of potent antibody responses.

Further, in collaboration with HVTN, we are preparing a number of phase I clinical studies to evaluate the safety and immunogenicity of the 2nd generation DNA and NYVAC and to select the optimal DNA and protein immunization schedule. The data will be instrumental for the design of the phase IIb efficacy study.

 

Project: Poxvirus T Cell Vaccine Discovery Consortium

Submitted January 31, 2011 (Interim Report)

The overall objective of PTVDC is to develop improved poxvirus-based vaccine candidates with increased immunogenicity by at least 10 fold in comparison to the conventional poxvirus vectors. To achieve this goal, the strategies implemented include: a) the deletion of virus-specific genes encoding proteins that have been implicated in the evasion of innate immune responses, b) the generation of replication competent (rc-) poxvirus vectors, and c) the generation of a combined (multiple gene deletion mutant plus replication competent) poxvirus vector.

In the past five years, we have successfully developed a series of new poxvirus vectors and identified the “best-in-class” replication competent vectors following a stringent selection algorithm with pre-defined criteria. This selection algorithm, containing a series of in vitro and in vivo testing’s, has been the result of a collective effort of our consortium and has demonstrated to be very effective in selecting candidate vaccines.

During the first half of the 6th year of our program, we have: 1) released two NYVAC GMP products; 2) completed the large NHP study comparing the priming ability of replication deficient NYVAC vs replication competent NYVAC-KC for protein boost with or without DNA. The immunogenicity data not only demonstrated that the new NYVAC vaccines developed within PTVDC are highly immunogenic both in terms of T-cell and B-cell response, but also provided new insight on the impact of different immunization regimens on immune responses. In the 2nd half of Year 6, we will initiate a number of new NHP studies to further evaluate and compare different vaccine combinations, inserts and regimens. The data from these NHP studies will be pivotal for the design of future clinical studies.

Project: Poxvirus-Based Vaccine Development

Submitted January 6, 2012 (Interim Report)
Submitted May 4, 2011
Submitted January 3, 2011
Submitted April 5, 2010

 

Project: Poxvirus T Cell Vaccine Discovery Consortium

Submitted January 31, 2011 (Interim Report)
Submitted September 13, 2010
Submitted February 5, 2010 (Interim Report)
Submitted September 15, 2009
Submitted February 1, 2009 (Interim Report)
Submitted September 1, 2008
Submitted January 31, 2008 (Interim Report)
Submitted September 1, 2007
 
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