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

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI049364-01
Application #
6546563
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2001-09-01
Project End
2006-08-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Pillai, Vinod Kumar Bhaskara; Kannanganat, Sunil; Penaloza-Macmaster, Pablo et al. (2011) Different patterns of expansion, contraction and memory differentiation of HIV-1 Gag-specific CD8 T cells elicited by adenovirus type 5 and modified vaccinia Ankara vaccines. Vaccine 29:5399-406
Sadagopal, Shanmugalakshmi; Amara, Rama Rao; Kannanganat, Sunil et al. (2008) Expansion and exhaustion of T-cell responses during mutational escape from long-term viral control in two DNA/modified vaccinia virus Ankara-vaccinated and simian-human immunodeficiency virus SHIV-89.6P-challenged macaques. J Virol 82:4149-53
Pillai, Vinod Bhaskara; Hellerstein, Michael; Yu, Tianwei et al. (2008) Comparative studies on in vitro expression and in vivo immunogenicity of supercoiled and open circular forms of plasmid DNA vaccines. Vaccine 26:1136-41
Nigam, Pragati; Earl, Patricia L; Americo, Jeffrey L et al. (2007) DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity and confers protection against a lethal monkeypox challenge. Virology 366:73-83
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Liu, Jinyan; Hellerstein, Michael; McDonnel, Michael et al. (2007) Dose-response studies for the elicitation of CD8 T cells by a DNA vaccine, used alone or as the prime for a modified vaccinia Ankara boost. Vaccine 25:2951-8
Kannanganat, Sunil; Kapogiannis, Bill G; Ibegbu, Chris et al. (2007) Human immunodeficiency virus type 1 controllers but not noncontrollers maintain CD4 T cells coexpressing three cytokines. J Virol 81:12071-6
Velu, Vijayakumar; Kannanganat, Sunil; Ibegbu, Chris et al. (2007) Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination. J Virol 81:5819-28
Robinson, H L (2007) HIV/AIDS vaccines: 2007. Clin Pharmacol Ther 82:686-93

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