Abstract

Given our understanding of envelope-based mechanisms of humoral evasion, we have attempted to design envelope-based immunogens with these mechanisms disabled. Such modied immunogens with weakened defenses may elicit more broadly neutralizing antibodies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005024-03
Application #
6987285
Study Section
(SBS)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Wu, Lan; Zhou, Tongqing; Yang, Zhi-yong et al. (2009) Enhanced exposure of the CD4-binding site to neutralizing antibodies by structural design of a membrane-anchored human immunodeficiency virus type 1 gp120 domain. J Virol 83:5077-86
Dey, Barna; Svehla, Krisha; Xu, Ling et al. (2009) Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog 5:e1000445
Morner, Andreas; Douagi, Iyadh; Forsell, Mattias N E et al. (2009) Human immunodeficiency virus type 1 env trimer immunization of macaques and impact of priming with viral vector or stabilized core protein. J Virol 83:540-51
Stricher, Francois; Huang, Chih-chin; Descours, Anne et al. (2008) Combinatorial optimization of a CD4-mimetic miniprotein and cocrystal structures with HIV-1 gp120 envelope glycoprotein. J Mol Biol 382:510-24
Dey, Barna; Pancera, Marie; Svehla, Krisha et al. (2007) Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. J Virol 81:5579-93
Douek, Daniel C; Kwong, Peter D; Nabel, Gary J (2006) The rational design of an AIDS vaccine. Cell 124:677-81
Pancera, Marie; Lebowitz, Jacob; Schon, Arne et al. (2005) Soluble mimetics of human immunodeficiency virus type 1 viral spikes produced by replacement of the native trimerization domain with a heterologous trimerization motif: characterization and ligand binding analysis. J Virol 79:9954-69
Burton, Dennis R; Desrosiers, Ronald C; Doms, Robert W et al. (2004) HIV vaccine design and the neutralizing antibody problem. Nat Immunol 5:233-6
Xiang, Shi-Hua; Kwong, Peter D; Gupta, Rishi et al. (2002) Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein. J Virol 76:9888-99
Yang, Xinzhen; Lee, Juliette; Mahony, Erin M et al. (2002) Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin. J Virol 76:4634-42