A Novel Replication Competent Flavivirus-based HIV Vaccine Platform ie RepliVax as a Priming Component for Improving Antibody Response

Project: Research project

Project Details

Description

A Novel Replication Competent Flavivirus-based HIV Vaccine Platform ie RepliVax as a Priming Component for Improving Antibody Response A Novel Replication Competent Flavivirus-based HIV Vaccine Platform, ie RepliVax, as a Priming Component for Improving Antibody Response Context: The development of an efficacious HIV vaccine is of paramount importance for the control and prevention of HIV infection. The RV-144 trial has shown a modest effect of the ALVAC-HIV (vCP1521) in combination with a recombinant gp120 subunit alum-adjuvanted vaccine (AIDSVAX B/E) in preventing infection, i.e. 31.2% efficacy thus providing evidence that an HIV vaccine may prevent HIV infection. Preliminary data from the immune correlates case control study from the RV-144 trial have shown that high plasma binding IgG antibody titers specific to Env V1/V2 are associated to reduced risk of infection. Therefore, the main focus of novel immunization strategies should be the substantial improvement of the vaccine-induced antibody response. The proposed project will build upon the large experience accumulated within the Poxvirus T-cell Vaccine Discovery Consortium under the CAVD program for development of the replication competent NYVAC vector and on additional specific competences on novel replicating viral vectors at Sanofi Pasteur. Preliminary data in Non Human Primates (NHPs) have shown that the replication competent NYVAC in combination with gp120 protein induced robust antibody responses (including V1/V2 IgG antibodies) Goals, Objectives and Key Milestones The primary goal of the proposed research project is to develop novel replication competent platforms for optimal priming of protein boosting and generation of protective antibody responses. Replication competent vectors will be investigated in prime/boost combination regimens with Env proteins alone or in combination with either replication deficient or other replication competent vectors in order to identify the optimal viral vector-based priming for Env protein boosting. The main objectives to achieve the primary goals include: 1) Development of a novel viral vector platform for delivering HIV antigens, i.e. RepliVax based on a replication competent, self-limiting flavivirus vector 2) Development of novel Env immunogens and delivery systems or adjuvant formulations for Env proteins 3) Comprehensive immunological characterization of the novel RepliVax vectors alone or in different prime/boost immunization strategies aim to enhancing antibody responses. The systematic analysis of different prime-boost regimens through a comprehensive in vitro and in vivo assessment of the immunological profile of the vaccine-induced immune responses will provide the scientific rationale for moving into clinical development a RepliVax-based HIV vaccine. The proposed project will also enlarge the portfolio of replication competent virus vector-based HIV vaccines and it has the potential to identify the best immunization regimen stimulating vigorous Env antibody responses associated to prevention of infection. The key milestones include: 1) Generation of three optimized RepliVax constructs expressing Env, Gag and Pol-Nef ready for NHP studies 2) Selection of the most promising DC targeting candidates to be moved forward in the prime-boost NHP study with RepliVax 3) Identification and generation of improved Env immunogen(s) with enhanced bNMAbs binding (either as antigens or as protein)
StatusFinished
Effective start/end date9/6/128/31/18

Funding

  • Gates (Bill and Melinda) Foundation: $671,044.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.