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

Abstract

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 [MID(50)]) 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 MID(50) (P < 0.0001), and contained acute CD4 loss at 15 MID(50) (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.

FIG. 1.

(A) Frequency of MHC class IB haplotypes in 112 monkeys vaccinated with Tat (full-colored bars) or controls (zebra-striped bars). (B and C) Analysis of CD4 T cells in chronic infection in viremic macaques (n = 71) stratified by treatment (vaccinated, n = 37; controls, n = 34) and challenge dose (10 to 15 MID₅₀, n = 58; 20 MID₅₀, n = 13) (B) or class IB haplotype (H1, n = 26; H2, n = 24; H3, n = 25; H4, n = 25; H5, n = 8; H6, n = 9) (C). On the abscissa is reported the difference in CD4 T-cell counts pre- and postchallenge; least-squares means with 95% confidence intervals are shown (analysis of variance model).