Beta-chemokine production in macaques vaccinated with live attenuated virus correlates with protection against simian immunodeficiency virus (SIVsm) challenge.

Abstract

Simian immunodeficiency virus (SIV) uses the CCR5 chemokine receptor as the main co-receptor to enter CD4 M cells. RANTES, MIP-1α and MIP-1β have been suggested as the major human immunodeficiency virus-suppressor factors produced by CD8 M T-cells. The aim of this study was to investigate the CD8 M T-cell production of anti-viral factors and of β-chemokines in six cynomolgus macaques vaccinated with live attenuated SIVmacC8 in relation to protection against infectious intrarectal SIVsm challenge. Three of the vaccinated animals were completely protected and one was partially protected against the challenge virus. Interestingly, these monkeys showed higher in vitro anti-viral CD8 M cell suppressor activity and β-chemokine production both before and after vaccination as compared to the infected monkeys. The results indicate that β-chemokines may play a role in protective immunity but also that genetic and/or environmental factors may influence their production.

The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

“…Thus, the betachemokine-mediated control of viral replication that occurs with in vitro PBMC culture systems does not appear to exist in the environment of an inflamed mucosa. This finding contrasts with other studies that have reported an association between in vitro beta-chemokine secretion by CD8 ϩ T cells in PBMC and vaccine-mediated protection from SIV-simian/HIV challenge (7,12,13,21,22,28,32,36).…”

“…c The animals in this group were treated on days 0, 3, 7, and 10, and vaginal lavages were collected on days Ϫ7, 0, 1,3,4,7,8,10,11,15,17,21, and 24. Vaginal lavages were collected 15 min prior to treatments on days when both procedures were performed.…”

Live, Attenuated Simian Immunodeficiency Virus SIVmac-M4, with Point Mutations in the Env Transmembrane Protein Intracytoplasmic Domain, Provides Partial Protection from Mucosal Challenge with Pathogenic SIVmac251

“…However, a direct correlation between CTL responses and protection of vaccinated animals from pathogenic challenge has not been demonstrated. In addition to MHC-restricted cytotoxicity, soluble factors, including MIP-1␣, MIP-1␤, and RANTES as well as undefined suppressor factors secreted by CD8 ϩ T cells, have been implicated in control of SIV replication (1,28,29). PBMC from macaques infected with live, attenuated SIVmac clones produced 8-to 10-fold more of these chemokines than uninfected controls.…”

Perforin-low memory CD8+cells are the predominant T cells in normal humans that synthesize the β-chemokine macrophage inflammatory protein-1β

“…This possibility is supported by three kinds of studies. First, production of ␤-chemokines by CD8 ϩ T cells correlates with protective immunity elicited by prototype HIV-1 vaccines in rhesus macaques (2)(3)(4)(5). Second, ␤-chemokines produced by peripheral blood mononuclear cells (6,7), CD8 ϩ T cells (8) activated with phytohemagglutinin A, or specific antigen (9) correlate with favorable prognosis in HIV-1 infection.…”