Monomeric HIV-1 gp120 exterior envelope glycoproteins have failed to efficiently elicit neutralizing antibodies. We have therefore attempted to reconstitute the trimeric native g120 structure as solid phase proteoliposomes (PLs) containing HIV envelope glycoproteins (EnvPLs). This study characterizes the native trimeric structure of the glycoproteins in a lipid bilayer environment and will test them as immunogens. Currently were are testing new versions from a more resistant primary isolate, cross-clade EnvPL versions as well as examining selected adjuvants in combination with the Env-PLs.? ? We will also reconstitute the 7-membrane spanning HIV-1 co-receptor molecules (CCR5 or CXCR4) in solid phase liposomes and assess their function to bind chemokine or HIV-1 gp120-CD4 complexes. We will also develop both a Biacore assay and a lipid-reconsituted ELISA (L-ELISA) to test binding of ligands to the co-receptor molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005025-07
Application #
7732748
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2008
Total Cost
$414,653
Indirect Cost
City
State
Country
United States
Zip Code
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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
Grundner, Christoph; Pancera, Marie; Kang, Joung-Mo et al. (2004) Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins. Virology 330:233-48
Grundner, Christoph; Mirzabekov, Tajib; Sodroski, Joseph et al. (2002) Solid-phase proteoliposomes containing human immunodeficiency virus envelope glycoproteins. J Virol 76:3511-21