This proposal characterizes CD4 independent strains of SIV with the goal of developing novel envelope based vaccines. In addition, we will characterize the humoral immune response generated in macaques immunized or infected with both CD4 dependent and CD4 independent viruses. Methods have been developed to analyze antibody blocking of envelope gpl20 with either the CD4 or CCR5 receptor molecules. We then propose to use the information gained from identification of determinants of CD4 independence in combination with that gained from immunization and infection studies to generate a vaccine that will more effectively expose the highly conserved and functionally critical coreceptor binding site. Finally, conformationally intact coreceptor molecules will be purified and mixed with these CD4 independent envelope proteins to generate """"""""triggered"""""""" envelopes that will also expose critical determinants of the gp41 subunit for immune recognition and hopefully elicit a productive neutralizing antibody response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI010577-03
Application #
6510067
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (01))
Program Officer
Bradac, James A
Project Start
2002-07-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$46,192
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pohlmann, Stefan; Munch, Jan; Aziz, Sheriff et al. (2007) A simian immunodeficiency virus V3 loop mutant that does not efficiently use CCR5 or common alternative coreceptors is moderately attenuated in vivo. Virology 360:275-85
Selvarajah, Suganya; Puffer, Bridget; Pantophlet, Ralph et al. (2005) Comparing antigenicity and immunogenicity of engineered gp120. J Virol 79:12148-63
Puffer, Bridget A; Altamura, Louis A; Pierson, Theodore C et al. (2004) Determinants within gp120 and gp41 contribute to CD4 independence of SIV Envs. Virology 327:16-25
Otto, Claas; Puffer, Bridget A; Pohlmann, Stefan et al. (2003) Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. Virology 315:292-302
Johnson, Welkin E; Morgan, Jennifer; Reitter, Julie et al. (2002) A replication-competent, neutralization-sensitive variant of simian immunodeficiency virus lacking 100 amino acids of envelope. J Virol 76:2075-86
Puffer, Bridget A; Pohlmann, Stefan; Edinger, Aimee L et al. (2002) CD4 independence of simian immunodeficiency virus Envs is associated with macrophage tropism, neutralization sensitivity, and attenuated pathogenicity. J Virol 76:2595-605