The only solution to the HIV epidemic in the developing world is a vaccine that either prevents infection or reduces transmission. We will define efficacious cellular immune responses against the AIDS virus and will attempt to engender these responses by vaccination. The correlates of protective immunity against HIV remain a mystery. To help resolve this mystery, we seek to identify which of the many different CD8+ lymphocyte responses present during the acute phase of AIDS virus infection actually contribute to reducing viral replication. We will identify at least five CD8+ lymphocyte epitopes for incorporation into a multi-epitope vaccine regimen. These epitopes should be recognized in the acute phase, induce CD8+ lymphocytes that efficiently control viral replication, and are derived from regions of the viral genome in which variation exacts a cost to viral fitness. We have developed two specific aims to address the hypothesis that effective CD8+ lymphocytes directed against at least five epitopes that are derived from regions under functional and structural constraints will control replication of SIV.
In Specific Aim I we will define efficacious CD8+ lymphocyte responses against epitopes derived from regions of the virus that are under functional constraints.
In Specific Aim II we will carry out vaccine efficacy experiments to engender the most efficacious CD8+ responses against epitopes defined in Specific Aim I.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049120-07
Application #
7217365
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
D'Souza, Patricia D
Project Start
2001-03-15
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
7
Fiscal Year
2007
Total Cost
$1,041,267
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Martins, Mauricio A; Wilson, Nancy A; Piaskowski, Shari M et al. (2014) Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239. J Virol 88:7493-516
Martins, Mauricio A; Bonaldo, Myrna C; Rudersdorf, Richard A et al. (2013) Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques. PLoS One 8:e54434
Reynolds, Matthew R; Weiler, Andrea M; Piaskowski, Shari M et al. (2012) A trivalent recombinant Ad5 gag/pol/nef vaccine fails to protect rhesus macaques from infection or control virus replication after a limiting-dose heterologous SIV challenge. Vaccine 30:4465-75
Vojnov, Lara; Martins, Mauricio A; Bean, Alexander T et al. (2012) The majority of freshly sorted simian immunodeficiency virus (SIV)-specific CD8(+) T cells cannot suppress viral replication in SIV-infected macrophages. J Virol 86:4682-7
Mudd, Philip A; Ericsen, Adam J; Burwitz, Benjamin J et al. (2012) Escape from CD8(+) T cell responses in Mamu-B*00801(+) macaques differentiates progressors from elite controllers. J Immunol 188:3364-70
Mudd, Philip A; Watkins, David I (2011) Understanding animal models of elite control: windows on effective immune responses against immunodeficiency viruses. Curr Opin HIV AIDS 6:197-201
Mudd, Philip A; Ericsen, Adam J; Walsh, Andrew D et al. (2011) CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission. J Virol 85:12804-10
Vojnov, Lara; Bean, Alexander T; Peterson, Eric J et al. (2011) DNA/Ad5 vaccination with SIV epitopes induced epitope-specific CD4? T cells, but few subdominant epitope-specific CD8? T cells. Vaccine 29:7483-90
Reed, Jason S; Sidney, John; Piaskowski, Shari M et al. (2011) The role of MHC class I allele Mamu-A*07 during SIV(mac)239 infection. Immunogenetics 63:789-807
Vojnov, Lara; Martins, Mauricio A; Almeida, Jorge R et al. (2011) GagCM9-specific CD8+ T cells expressing limited public TCR clonotypes do not suppress SIV replication in vivo. PLoS One 6:e23515

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