Abstract

The principal investigator proposes to employ a pathogenic chimeric simian-human immunodeficiency virus (SHIV) to determine whether passive immunization can protect against mucosa (vaginal) or needle stick exposure to HIV. Two sources of SHIV/HIV-neutralizing antibody will be evaluated: a monoclonal anti-HIV gp120 (mAb b12) or polyconal anti-SHIV pooled sera from infected rhesus macaques with low virus burdens. Passive immunotherapy will be initiated either 12 hours pre- or 12 hours post intravaginal SHIV exposure and 10 pre- or 1 or 12 hours post subcutaneous injection. The establishment of infection and disease progression will then be monitored over a 12 month period and compared with animals not receiving passive immunization. The results of these studies are designed to establish whether passive immunization with virus neutralizing antibody can prevent or abort SHIV infection or influence the progression of SHIV disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040372-03
Application #
2837468
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Bradac, James A
Project Start
1996-12-01
Project End
1999-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Kansas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160

  Publications

David, S A; Smith, M S; Lopez, G J et al. (2001) Selective transmission of R5-tropic HIV type 1 from dendritic cells to resting CD4+ T cells. AIDS Res Hum Retroviruses 17:59-68
Raghavan, R; Cheney, P D; Raymond, L A et al. (1999) Morphological correlates of neurological dysfunction in macaques infected with neurovirulent simian immunodeficiency virus. Neuropathol Appl Neurobiol 25:285-94
Joag, S V; Li, Z; Wang, C et al. (1999) Passively administered neutralizing serum that protected macaques against infection with parenterally inoculated pathogenic simian-human immunodeficiency virus failed to protect against mucosally inoculated virus. AIDS Res Hum Retroviruses 15:391-4
Narayan, S V; Mukherjee, S; Jia, F et al. (1999) Characterization of a neutralization-escape variant of SHIVKU-1, a virus that causes acquired immune deficiency syndrome in pig-tailed macaques. Virology 256:54-63
Joag, S V; Liu, Z Q; Stephens, E B et al. (1998) Oral immunization of macaques with attenuated vaccine virus induces protection against vaginally transmitted AIDS. J Virol 72:9069-78
Joag, S V; Li, Z; Wang, C et al. (1998) Chimeric SHIV that causes CD4+ T cell loss and AIDS in rhesus macaques. J Med Primatol 27:59-64
Foresman, L; Jia, F; Li, Z et al. (1998) Neutralizing antibodies administered before, but not after, virulent SHIV prevent infection in macaques. AIDS Res Hum Retroviruses 14:1035-43
Cole, K S; Murphey-Corb, M; Narayan, O et al. (1998) Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections. J Virol 72:7852-9
Joag, S V; Li, Z; Foresman, L et al. (1997) Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques. AIDS Res Hum Retroviruses 13:635-45
Joag, S V; Adany, I; Li, Z et al. (1997) Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS. J Virol 71:4016-23