Immunization strategies using DNA priming and recombinant Modified Vaccinia Ankara (MVA) boosters have proved to raise broad and high titer T-cell responses in preclinical models. The goals of this IPCAVD are to evaluate the ability of DNA/MVA vaccines for human immunodeficiency virus to generate vaccines for cross-clade immune responses. This project will provide data on whether worldwide vaccination can be accomplished with a single DNA/MVA immunogen, or whether a mixture of DNA/MVA immunogens will be required. This project includes: assay development diagnostic and immune assay standardization, and Phase 1 human trials.
The specific aims are: 1. Develop and optimize T-cell assays to measure HIV specific immune responses in HIV-1 DNA/MVA vaccines to be quantitative, sensitive, high throughput, field adaptable and capable of measuring the breadth of responses to subtype A/G and B vaccines. 2. To test the validity of molecular diagnostic techniques for detecting HIV in patients with Clade B and Clade A infection, and to optimize detection of HIV infection for vaccinees who may have low level viral replication due to strong cytotoxic T-cell responses. 3. To test HIV clade B and IbNG-like AG vaccines, singly and in combination, with an MVA boost for their ability to generate high levels of intra-clade and cross-clade ELISPOT responses.
Specific Aim 1 & 2 will involve participants in both the United States and in the Ivory Coast (through our CDC collaboration).
For Specific Aim 3, three Phase 1-vaccine protocols will test the safety and immunogenicity of single, mixed and formulated DNA/MVA vaccines. Each of these will be preceded by protocols establishing the safety of the proposed MVA boosters, and of a formulation designed to increase the efficiency of DNA priming. The goals of these trials are to provide seminal data regarding the need for clade specific vaccines, and to establish the foundation for further Phase II/III testing of DNA/MVA vaccines
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