Abstract

The extreme genetic diversity of HIV-1 isolates poses a major challenge for the development of an HIV vaccine. Recent studies in mice have suggested that using """"""""centralized"""""""" HIV-1 sequences in immunogens may be an effective strategy for minimizing the impact of this genetic diversity on the creation of effective vaccines. Simian immunodeficiency virus (SIV) and the simian human immunodeficiency virus (SHIV) infected rhesus monkeys provide a powerful model for evaluating potential HIV vaccine strategies. We will employ this animal model to explore the use of """"""""centralized"""""""" gene-based HIV-1 vaccine strategies for broadening the recognition specificity of vaccine-elicited immune responses. Specifically, we will use this model to explore the: 1. Selection of an optimal """"""""centralized"""""""" HIV-1 envelope immunogen. 2. Comparison of """"""""centralized"""""""" and contemporary HIV-1 gag-pol-nef immunogens. 3. Comparison of """"""""centralized"""""""" and multiclade HIV-1 immunogens 4. Assessment of recombinant MVA """"""""centralized"""""""" HIV-1 immunogens. 5. Evaluation of """"""""centralized"""""""" envelope subunit immunogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI061734-03
Application #
7404465
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$935,034
Indirect Cost

  Institution

Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Pincus, Seth H; Song, Kejing; Maresh, Grace A et al. (2017) Identification of Human Anti-HIV gp160 Monoclonal Antibodies That Make Effective Immunotoxins. J Virol 91:
Pincus, Seth H; Song, Kejing; Maresh, Grace A et al. (2017) Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160. J Virol 91:
Go, Eden P; Liao, Hua-Xin; Alam, S Munir et al. (2013) Characterization of host-cell line specific glycosylation profiles of early transmitted/founder HIV-1 gp120 envelope proteins. J Proteome Res 12:1223-34
Go, Eden P; Hewawasam, Geetha; Liao, Hua-Xin et al. (2011) Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry. J Virol 85:8270-84
Liao, Hua-Xin; Chen, Xi; Munshaw, Supriya et al. (2011) Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med 208:2237-49
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
Barouch, Dan H; O'Brien, Kara L; Simmons, Nathaniel L et al. (2010) Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med 16:319-23
Lu, Xiaozhi; Hora, Bhavna; Cai, Fangping et al. (2010) Generation of random mutant libraries with multiple primers in a single reaction. J Virol Methods 167:146-51
Tomaras, Georgia D; Haynes, Barton F (2010) Strategies for eliciting HIV-1 inhibitory antibodies. Curr Opin HIV AIDS 5:421-7
Salazar-Gonzalez, Jesus F; Salazar, Maria G; Keele, Brandon F et al. (2009) Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med 206:1273-89

Showing the most recent 10 out of 27 publications