Abstract

Heterologous prime/boost immunization using DNA priming and recombinant MVA boosters have proved to raise much higher levels of T-cell responses than either of these modalities of immunization alone. The goals of this program project are to develop and evaluate the cross-clade activity of DNA/MVA protocols for immunodeficiency virus vaccines. The charges for Project 1 are to provide DNA and MVA immunogens for the preclinical and clinical trials supported by Projects 2 and 3. Two major goals for Project 1 are to develop immunogens that increase the efficiency of DNA priming and MVA boosters and to construct immunogens that allow evaluation of cross-clade responses. To increase the immunogenicity of vaccine DNAs, plasmids will be optimized for expression in the presence of interferons (IFN), and vaccine inserts will be codon optimized. Both clade A and clade B immunogens will be built to facilitate the analysis of cross-clade responses. A team of Emory, CDC and NIAID investigators will accomplish Project 1. Drs. Smith, Robinson, and Boss (Emory) will be responsible for the construction of the DNA immunogens, Dr. Moss (NIAID) will be responsible for the construction of MVA immunogens, and Dr. Folks (CDC) will provide clade A sequences and conduct safety tests.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI049364-01
Application #
6546561
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

  Institution

Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

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
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
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
Lai, Lilin; Vodros, Dalma; Kozlowski, Pamela A et al. (2007) GM-CSF DNA: an adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine. Virology 369:153-67
Robinson, Harriet L; Sharma, Sunita; Zhao, Jun et al. (2007) Immunogenicity in macaques of the clinical product for a clade B DNA/MVA HIV vaccine: elicitation of IFN-gamma, IL-2, and TNF-alpha coproducing CD4 and CD8 T cells. AIDS Res Hum Retroviruses 23:1555-62
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
Kannanganat, Sunil; Ibegbu, Chris; Chennareddi, Lakshmi et al. (2007) Multiple-cytokine-producing antiviral CD4 T cells are functionally superior to single-cytokine-producing cells. J Virol 81:8468-76

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