Although live attenuated vaccine strains of simian immunodeficiency virus (SIV) have proven highly effective in protecting macaques against challenge with pathogenic SIV strains, little is known about the mechanisms of protective immunity induced by these vaccines. We examined cytotoxic T lymphocyte (CTL) responses against SIV in animals infected with SIVmac239?nef (deficient in nef) or SIVmac239?3 (deficient in nef, vpr and upstream sequences in U3). To enhance detection of SIV-specific CTL activity, we stimulated peripheral blood mononuclear cells with autologous B lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing SIV proteins and subsequently inactivated with psoralen and UV light. Animals chronically infected with SIV239?nef or SIV239?3 mounted vigorous CTL responses against the SIV gag and envelope proteins. This CTL activity was MHC-restricted and mediated by CD8+ T lymphocytes. CTL responses persisted at relatively high levels for more than six years after infection. Limiting dilution precursor frequency assays demonstrated that the frequency of SIV-specific CTL was as high as 234 CTL precursors per 100,000 cells. Animals acutely infected with SIV239?nef developed CTL activity by day 14 after infection, coincident with decreases in viral load. Animals acutely infected with SIV239?3 developed CTL responses within four weeks of infection. Thus, vaccination of juvenile or adult animals with SIV239?nef or SIV239?3 results in the induction of a vigorous CTL response which arises early in the course of infection and persists for years after a single inoculation of virus.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000168-37
Application #
6277772
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519
Arcaro, Michael J; Livingstone, Margaret S (2017) A hierarchical, retinotopic proto-organization of the primate visual system at birth. Elife 6:
McLean, Will J; Yin, Xiaolei; Lu, Lin et al. (2017) Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells. Cell Rep 18:1917-1929

Showing the most recent 10 out of 365 publications