Abstract

Based on 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. We have also devised scaffolding technology, as a means of presenting structural mimics of the epitopes of broadly neutralizing antibodies to assist in their re-elicitation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005024-05
Application #
7299829
Study Section
(SBS)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2006
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