Failures to date in our effort to create an effective AIDS vaccine can be explained, at least in part, by two shortcomings: (1) a lack of appreciation of the potential importance of virus-specific cell-mediated immunity in preventing HIV-1 infection, and (2) an inability to overcome the problem of viral diversity. Recent advances in our understanding of vaccine technologies that can elicit effector T cell responses and the development of important new non-human primate model systems for studying AIDS vaccine development make it possible now to begin addressing some of these issues in a meaningful way. We have shown now that peptides, live recombinant organisms and plasmid DNA can licit AIDS virus-specific CTL in higher primate species. We have also developed a chimeric virus expressing a primary patient HIV-1 envelope on an SIVmac backbone that can infect and induce AIDS in macaque species. These tools will be harnessed in the proposed studies to explore in rhesus monkeys: 1. HIV-1 envelope V3 loop peptide-elicited immunity 2. Vaccination to broaden CTL recognition of variant viruses 3. Cytokine profiles of CD4+ T cells following infections and vaccinations 4. Novel HIV vaccine strategies.

Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
8
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Kirchherr, Jennifer L; Hamilton, Jennifer; Lu, Xiaozhi et al. (2011) Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120. Virology 409:163-74
Gao, Feng; Liao, Hua-Xin; Hahn, Beatrice H et al. (2007) Centralized HIV-1 envelope immunogens and neutralizing antibodies. Curr HIV Res 5:572-7
Nordone, Sushila K; Peacock, James W; Kirwan, Shaun M et al. (2006) Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of nasally administered peptide vaccines. AIDS Res Hum Retroviruses 22:558-68
Gao, Feng; Korber, Bette T; Weaver, Eric et al. (2004) Centralized immunogens as a vaccine strategy to overcome HIV-1 diversity. Expert Rev Vaccines 3:S161-8
Peacock, James W; Nordone, Sushila K; Jackson, Shawn S et al. (2004) Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting. J Virol 78:13163-72
Liao, Hua Xin; Cianciolo, George J; Staats, Herman F et al. (2002) Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Vaccine 20:2396-403
Bradney, Curtis P; Sempowski, Gregory D; Liao, Hua-Xin et al. (2002) Cytokines as adjuvants for the induction of anti-human immunodeficiency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization. J Virol 76:517-24
Staats, H F; Bradney, C P; Gwinn, W M et al. (2001) Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. J Immunol 167:5386-94