Abstract

In this study, we have produced soluble versions of Env glycoproteins derived from a primary isolate stabilized by Phe 43 pocket filling mutations and inter-domain cysteine bonds. We have tested these glycoproteins for immunogenicity in rabbits as a prime for soluble gp140 molecule boost. Breadth of neutralization indicate that these glycoproteins significantly increase neutralization breadth as a prime for the soluble gp140 trimer boosts and both are interesting platforms for further modification to better elicit 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 #
1Z01AI005078-01
Application #
7189318
Study Section
(VRC)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

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

  Publications

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
Wu, Xueling; Zhou, Tongqing; O'Dell, Sijy et al. (2009) Mechanism of human immunodeficiency virus type 1 resistance to monoclonal antibody B12 that effectively targets the site of CD4 attachment. J Virol 83:10892-907
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
Zhou, Tongqing; Xu, Ling; Dey, Barna et al. (2007) Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445:732-7
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
Grundner, Christoph; Li, Yuxing; Louder, Mark et al. (2005) Analysis of the neutralizing antibody response elicited in rabbits by repeated inoculation with trimeric HIV-1 envelope glycoproteins. Virology 331:33-46
Pancera, Marie; Wyatt, Richard (2005) Selective recognition of oligomeric HIV-1 primary isolate envelope glycoproteins by potently neutralizing ligands requires efficient precursor cleavage. Virology 332:145-56
Koch, Markus; Frazier, James; Sodroski, Joseph et al. (2005) Characterization of antibody responses to purified HIV-1 gp120 glycoproteins fused with the molecular adjuvant C3d. Virology 340:277-84

Showing the most recent 10 out of 14 publications