Transient viremia appearing after SHIV 89.6 infection evoked humor and cellular immune responses to SIV that protected against subsequent intravaginal SIV challenge. The presence of SIV specific CTLs in peripheral blood correlated with resistance to pathogenic SIV challenge. Because the vaccination regimen provided protection from pathogenic virus challenge and because the vaccine virus and challenge virus genes can be easily distinguished by PCR, this system provides an excellent opportunity to determine the mechanism of protection from challenge. The investigators will focus on traditional immune effector mechanisms, CD4+ T cell cytokine secretion patterns, and chemokine levels in immunized animals. Further they will determine if immune responses to viral regulatory gene products in the SHIV immunized animals are associated with protection from challenge. Important aspects of the proposed studies include experiments that determine if the route of SHIV immunization affects the ability of the animals to resist vaginal challenge with pathogenic SIV. This will determine whether stimulation of genital immune responses is necessary for protection against vaginal challenge. Subunit, immunization and VLP immunization strategies will be attempted to elicit mucosal and systemic immune responses comparable to those observed in animals immunized with nonpathogenic SHIV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI035545-06
Application #
2837439
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Bradac, James A
Project Start
1993-11-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Other Domestic Higher Education
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Miller, Christopher J; Lu, Fabien X (2003) Anti-HIV and -SIV immunity in the vagina. Int Rev Immunol 22:65-76
Lena, P; Villinger, F; Giavedoni, L et al. (2002) Co-immunization of rhesus macaques with plasmid vectors expressing IFN-gamma, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus. Vaccine 20 Suppl 4:A69-79
Abel, Kristina; Alegria-Hartman, Michelle J; Rothaeusler, Kristina et al. (2002) The relationship between simian immunodeficiency virus RNA levels and the mRNA levels of alpha/beta interferons (IFN-alpha/beta) and IFN-alpha/beta-inducible Mx in lymphoid tissues of rhesus macaques during acute and chronic infection. J Virol 76:8433-45
Marthas, M L; Lu, D; Penedo, M C et al. (2001) Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses. AIDS Res Hum Retroviruses 17:1455-66
Greenier, J L; Miller, C J; Lu, D et al. (2001) Route of simian immunodeficiency virus inoculation determines the complexity but not the identity of viral variant populations that infect rhesus macaques. J Virol 75:3753-65
Abel, K; Alegria-Hartman, M J; Zanotto, K et al. (2001) Anatomic site and immune function correlate with relative cytokine mRNA expression levels in lymphoid tissues of normal rhesus macaques. Cytokine 16:191-204
Huang, Y T; Miller, C J; Wong, V et al. (1999) Replication and budding of simian immunodeficiency virus in polarized epithelial cells. Virology 257:24-34
Miller, C J; Hu, J (1999) T cell-tropic simian immunodeficiency virus (SIV) and simian-human immunodeficiency viruses are readily transmitted by vaginal inoculation of rhesus macaques, and Langerhans' cells of the female genital tract are infected with SIV. J Infect Dis 179 Suppl 3:S413-7
Lu, X; Kiyono, H; Lu, D et al. (1998) Targeted lymph-node immunization with whole inactivated simian immunodeficiency virus (SIV) or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIVmac251. AIDS 12:1-10
McChesney, M B; Collins, J R; Lu, D et al. (1998) Occult systemic infection and persistent simian immunodeficiency virus (SIV)-specific CD4(+)-T-cell proliferative responses in rhesus macaques that were transiently viremic after intravaginal inoculation of SIV. J Virol 72:10029-35

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