Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.

Published

Journal Article

With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.

Full Text

Duke Authors

Cited Authors

  • Barouch, DH; Santra, S; Schmitz, JE; Kuroda, MJ; Fu, TM; Wagner, W; Bilska, M; Craiu, A; Zheng, XX; Krivulka, GR; Beaudry, K; Lifton, MA; Nickerson, CE; Trigona, WL; Punt, K; Freed, DC; Guan, L; Dubey, S; Casimiro, D; Simon, A; Davies, ME; Chastain, M; Strom, TB; Gelman, RS; Montefiori, DC; Lewis, MG; Emini, EA; Shiver, JW; Letvin, NL

Published Date

  • October 2000

Published In

Volume / Issue

  • 290 / 5491

Start / End Page

  • 486 - 492

PubMed ID

  • 11039923

Pubmed Central ID

  • 11039923

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.290.5491.486

Language

  • eng