Impact of Viral Dose and Major Histocompatibility Complex Class IB Haplotype on Viral Outcome in Mauritian Cynomolgus Monkeys Vaccinated with Tat upon Challenge with Simian/Human Immunodeficiency Virus SHIV89.6P

被引:26
作者
Cafaro, Aurelio [1 ]
Bellino, Stefania [1 ]
Titti, Fausto [1 ]
Maggiorella, Maria Teresa [1 ]
Sernicola, Leonardo [1 ]
Wiseman, Roger W. [2 ,3 ]
Venzon, David [4 ]
Karl, Julie A. [2 ,3 ]
O'Connor, David [2 ,3 ]
Monini, Paolo [1 ]
Robert-Guroff, Marjorie [5 ,6 ]
Ensoli, Barbara [1 ]
机构
[1] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy
[2] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA
[3] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA
[4] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA
[5] NIH, Vaccine Branch, Bethesda, MD 20892 USA
[6] NCI, NIH, Bethesda, MD 20892 USA
关键词
HIV-INFECTION; SIV-GAG; MACAQUES; REPLICATION; PROTEIN; PROGRESSION; DISEASE; TRIAL; AIDS;
D O I
10.1128/JVI.00377-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The effects of the challenge dose and major histocompatibility complex (MHC) class IB alleles were analyzed in 112 Mauritian cynomolgus monkeys vaccinated (n = 67) or not vaccinated (n = 45) with Tat and challenged with simian/human immunodeficiency virus (SHIV) 89.6P(cy243). In the controls, the challenge dose (10 to 20 50% monkey infectious doses [MID50]) or MHC did not affect susceptibility to infection, peak viral load, or acute CD4 T-cell loss, whereas in the chronic phase of infection, the H1 haplotype correlated with a high viral load (P = 0.0280) and CD4 loss (P = 0.0343). Vaccination reduced the rate of infection acquisition at 10 MID50 (P < 0.0001), and contained acute CD4 loss at 15 MID50 (P = 0.0099). Haplotypes H2 and H6 were correlated with increased susceptibility (P = 0.0199) and resistance (P = 0.0087) to infection, respectively. Vaccination also contained CD4 depletion (P = 0.0391) during chronic infection, independently of the challenge dose or haplotype.
引用
收藏
页码:8953 / 8958
页数:6
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