Abstract

The overall objective of this proposal is to identify correlates of protection against vaginal transmission of HIV-1 in an animal model. Cervical, vaginal and lymphatic tisues (LTs) from rhesus macaques vaccinated with an attenuated SHIV vaccine who were or were not protected in a subsequent challenge with SIV will be compared. In situ technologies (hybridization, immunohistochemical and tetramer staining) will be used to test 3 hypotheses: 1) protection will correlate with diminished immune activation and activated CD4+ cell targets for virus replication; 2) protection will correlate with high in vivo effector: target ratios of SIV-specific CD8+ T cells : SIV RNA+ cells; 3) protection will correlate with a diminished early immunosuppressive response to infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI066314-03
Application #
7454448
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$524,564
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Ciupe, Stanca M; Miller, Christopher J; Forde, Jonathan E (2018) A Bistable Switch in Virus Dynamics Can Explain the Differences in Disease Outcome Following SIV Infections in Rhesus Macaques. Front Microbiol 9:1216
Fieni, Francis; Stone, Mars; Ma, Zhong-Min et al. (2013) Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation. PLoS One 8:e76367
McChesney, Michael B; Miller, Christopher J (2013) New directions for HIV vaccine development from animal models. Curr Opin HIV AIDS 8:376-81
Rothaeusler, Kristina; Ma, Zhong-Min; Qureshi, Huma et al. (2012) Antiviral antibodies and T cells are present in the foreskin of simian immunodeficiency virus-infected rhesus macaques. J Virol 86:7098-106
Genescà, Meritxell; Ma, Zhong-Min; Wang, Yichuan et al. (2012) Live-attenuated lentivirus immunization modulates innate immunity and inflammation while protecting rhesus macaques from vaginal simian immunodeficiency virus challenge. J Virol 86:9188-200
Genescà, Meritxell; McChesney, Michael B; Miller, Christopher J (2010) Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus. PLoS One 5:e9814
Stone, Mars; Keele, Brandon F; Ma, Zhong-Min et al. (2010) A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol 84:7083-95
Vaidya, Naveen K; Ribeiro, Ruy M; Miller, Christopher J et al. (2010) Viral dynamics during primary simian immunodeficiency virus infection: effect of time-dependent virus infectivity. J Virol 84:4302-10
Lozano Reina, José-Manuel; Favre, David; Kasakow, Zeljka et al. (2009) Gag p27-specific B- and T-cell responses in Simian immunodeficiency virus SIVagm-infected African green monkeys. J Virol 83:2770-7
Genescà, M; McChesney, M B; Miller, C J (2009) Antiviral CD8+ T cells in the genital tract control viral replication and delay progression to AIDS after vaginal SIV challenge in rhesus macaques immunized with virulence attenuated SHIV 89.6. J Intern Med 265:67-77

Showing the most recent 10 out of 23 publications