With more than 30 million HIV-infected individuals, there can be few other more pressing biomedical priorities than to produce an effective vaccine for HIV. Given the important role that cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) play in controlling viral replication, it is critical that this vaccine stimulates these cellular responses. Current methods of detecting vaccine-induced immune responses include Intra-Cellular Cytokine Staining (ICS), Enzyme-Linked Spot-Forming Assays (ELISPOT), and tetramer staining. ICS and ELISPOT can be carried out using peptides of 10-15 amino acids in length. However, depending on where the true epitope lies in the synthetic peptide, these peptide sets may not accurately detect the magnitude of the immune response. The identification of minimal optimal epitopes is the best method to accurately assess cellular immune responses. Furthermore, the synthesis of tetramers is absolutely dependent on knowledge of the minimal optimal epitope. Finally, we recently discovered that there are several MHC class l-restricted epitopes in SIV cryptic Open Reading Frames (cORFs). We, therefore, propose to continue our definition of minimal optimal epitopes for common Indian rhesus macaque class I and II molecules in both classical and cryptic ORFs in SIV.

Public Health Relevance

(provided by applicant): SIV infection in Indian rhesus macaques is the best animal model for studying HIV-infected humans. SIV challenge of vaccinated Indian rhesus macaques is one of the best defined models available for pre-clinical development of HIV vaccines. Identification of MHC alleles and definition of SIV-specific epitopes is critical in the definition of the immune response in this biomedically important system.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
7R24RR015371-13
Application #
8413903
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Harding, John D
Project Start
2000-07-01
Project End
2014-06-30
Budget Start
2012-03-20
Budget End
2012-06-30
Support Year
13
Fiscal Year
2011
Total Cost
$350,757
Indirect Cost
Name
University of Miami School of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
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
Mudd, Philip A; Martins, Mauricio A; Ericsen, Adam J et al. (2012) Vaccine-induced CD8+ T cells control AIDS virus replication. Nature 491:129-33
Sette, Alessandro; Sidney, John; Southwood, Scott et al. (2012) A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules. Immunogenetics 64:421-34
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; Ericsen, Adam J; Price, Andrew A et al. (2011) Reduction of CD4+ T cells in vivo does not affect virus load in macaque elite controllers. J Virol 85:7454-9
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
Reynolds, Matthew R; Sacha, Jonah B; Weiler, Andrea M et al. (2011) The TRIM5{alpha} genotype of rhesus macaques affects acquisition of simian immunodeficiency virus SIVsmE660 infection after repeated limiting-dose intrarectal challenge. J Virol 85:9637-40
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
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

Showing the most recent 10 out of 50 publications