Despite intensive study, the immune responses associated with protective immunity against HIV infection remain poorly understood. Immunization with attenuated SIV strains has proven to be one of the most effective means to induce protection in nonhuman primates, and analysis of protective immunity in this model thus offers an ideal research setting in which to define specific mechanisms that may play a role in mediating protection. Work conducted in the previous funding period has provided a detailed description of the array of immune responses induced by attenuated SIV and provided correlative evidence for roles for both cellular and humoral immune responses in protecting against infection with pathogenic SIV strains. However, increasing evidence suggests that identification of the mechanisms of protection in this model is likely to be complex, is likely to represent the contributions of multiple arms of the immune system and may vary depending on the challenge model and host genotype. The overall goal of the current proposal is to further dissect the relative roles of cellular and humoral immune responses in mediating protection induced by live attenuated SIV strains.
Specific aims i nclude: 1. To examine the role of CD8+ T cell responses in mediating protection against vaginal challenge in SIVmac239delta3-vaccinated macaques. 2. To examine the relative contributions of cellular and humoral immune responses in mediating protection against intravenous challenge in (3-vaccinated macaques. 3. To carry out a detailed examination of early virologic and immunologic events occurring following intravenous challenge of macaques immunized with attenuated SIV. 4. To examine the evolution of CD8+ T cell responses in delta3-vaccinated macaques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI062412-03
Application #
7080447
Study Section
Special Emphasis Panel (ZRG1-AARR-C (02))
Program Officer
Miller, Nancy R
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$626,106
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Reeves, R Keith; Evans, Tristan I; Fultz, Patricia N et al. (2011) Potential confusion of contaminating CD16+ myeloid DCs with anergic CD16+ NK cells in chimpanzees. Eur J Immunol 41:1070-4
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Salisch, Nadine C; Kaufmann, Daniel E; Awad, Amany S et al. (2010) Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J Immunol 184:476-87
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Mansfield, Keith; Lang, Sabine M; Gauduin, Marie-Claire et al. (2008) Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. J Virol 82:4135-48
Gauduin, Marie-Claire; Yu, Yi; Barabasz, Amy et al. (2006) Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection. J Exp Med 203:2661-72
Macchia, Iole; Gauduin, Marie-Claire; Kaur, Amitinder et al. (2006) Expression of CD8alpha identifies a distinct subset of effector memory CD4+ T lymphocytes. Immunology 119:232-42

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