The goal of this proposal will be to probe the HIV-1 specific B cell repertoire of rhesus monkeys infected with chimeric simian-human immunodeficiency viruses (SHIVs) by developing a large panel of rhesus monoclonal antibodies (RhMAbs) that recognize envelope glycoproteins of HIV-1. The RhMAbs will be characterized with respect to epitope mapping, strain reactivity, and functional activity in vitro. The rhesus Mabs will be compared with our existing panel of human MAbs to HIV-1 surface glycoproteins in order to determine to what extent B cell responses elicited in SHIV infected monkeys are the same or different from that occurring in patients infected with HIV-1. This is an important question which bears on the relevancy of the SHIV model to studies of HIV-1 pathogenesis and vaccine efficacy to human disease. In addition, rhesus MAbs that have particularly potent neutralizing activity against HIV-1 in vitro can be used in a carefully modeled system to determine whether such antibodies are capable to protecting naïve monkeys from challenge with pathogenic SHIVs. Finally, novel MAbs may be developed which are quite different from HMAbs generated from HIV-1 infected patients and these MAbs have usefulness in further investigations of the structure and function of HIV-1 envelope glycoproteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI046275-02
Application #
6170917
Study Section
Special Emphasis Panel (ZRG1-AARR-2 (01))
Program Officer
Bradac, James A
Project Start
1999-06-01
Project End
2004-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
2
Fiscal Year
2000
Total Cost
$220,613
Indirect Cost
Name
Tulane University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Robinson, Harriet L; Montefiori, David C; Villinger, Francois et al. (2006) Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine. Virology 352:285-94
Ellis, Brett R; Munene, Elephas; Elliott, Debra et al. (2004) Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis) in Kenya. Retrovirology 1:34