An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells.

Published

Journal Article

BACKGROUND: Current efforts to develop HIV vaccines that seek to stimulate immune responses have been disappointing, underscoring the inability of natural immune responses to control HIV-1 infection. Here we tested an alternative strategy to induce anti-HIV immune responses by inhibiting a host's natural immune inhibitor. METHODS AND FINDINGS: We used small interfering RNA (siRNA) to inhibit suppressor of cytokine signaling (SOCS) 1, a key negative regulator of the JAK/STAT pathway, and investigated the effect of this silencing on the ability of dendritic cells (DCs) to induce anti-HIV-1 immunity. We found that SOCS1-silenced DCs broadly induced enhanced HIV-1 envelope (Env)-specific CD8+ cytotoxic T lymphocytes and CD4+ T helper cells, as well as antibody responses, in mice. Importantly, SOCS1-silenced DCs were more resistant to HIV Env-mediated suppression and were capable of inducing memory HIV Env-specific antibody and T cell responses. SOCS1-restricted signaling, as well as production of proinflammatory cytokines such as interleukin-12 by DCs, play a critical role in regulating the anti-HIV immune response. Furthermore, the potency of HIV DNA vaccination is significantly enhanced by coimmunization with SOCS1 siRNA expressor DNA. CONCLUSIONS: This study demonstrates that SOCS1 functions as an antigen presentation attenuator to control both HIV-1-specific humoral and cellular responses. This study represents the first, to our knowledge, attempt to elicit HIV-specific T cell and antibody responses by inhibiting a host's antigen presentation attenuator, which may open a new and alternative avenue to develop effective therapeutic and prophylactic HIV vaccines.

Full Text

Duke Authors

Cited Authors

  • Song, X-T; Evel-Kabler, K; Rollins, L; Aldrich, M; Gao, F; Huang, XF; Chen, S-Y

Published Date

  • January 2006

Published In

Volume / Issue

  • 3 / 1

Start / End Page

  • e11 -

PubMed ID

  • 16381597

Pubmed Central ID

  • 16381597

Electronic International Standard Serial Number (EISSN)

  • 1549-1676

Digital Object Identifier (DOI)

  • 10.1371/journal.pmed.0030011

Language

  • eng

Conference Location

  • United States