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

Publication ,  Journal Article
Song, X-T; Evel-Kabler, K; Rollins, L; Aldrich, M; Gao, F; Huang, XF; Chen, S-Y
Published in: PLoS Med
January 2006

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.

Duke Scholars

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Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

January 2006

Volume

3

Issue

1

Start / End Page

e11

Location

United States

Related Subject Headings

  • Vaccination
  • T-Lymphocytes
  • Suppressor of Cytokine Signaling Proteins
  • Suppressor of Cytokine Signaling 1 Protein
  • Receptors, Interleukin-12
  • RNA, Small Interfering
  • RNA Interference
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

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Song, X.-T., Evel-Kabler, K., Rollins, L., Aldrich, M., Gao, F., Huang, X. F., & Chen, S.-Y. (2006). An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells. PLoS Med, 3(1), e11. https://doi.org/10.1371/journal.pmed.0030011
Song, Xiao-Tong, Kevin Evel-Kabler, Lisa Rollins, Melissa Aldrich, Feng Gao, Xue F. Huang, and Si-Yi Chen. “An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells.PLoS Med 3, no. 1 (January 2006): e11. https://doi.org/10.1371/journal.pmed.0030011.
Song X-T, Evel-Kabler K, Rollins L, Aldrich M, Gao F, Huang XF, et al. An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells. PLoS Med. 2006 Jan;3(1):e11.
Song, Xiao-Tong, et al. “An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells.PLoS Med, vol. 3, no. 1, Jan. 2006, p. e11. Pubmed, doi:10.1371/journal.pmed.0030011.
Song X-T, Evel-Kabler K, Rollins L, Aldrich M, Gao F, Huang XF, Chen S-Y. An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells. PLoS Med. 2006 Jan;3(1):e11.

Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

January 2006

Volume

3

Issue

1

Start / End Page

e11

Location

United States

Related Subject Headings

  • Vaccination
  • T-Lymphocytes
  • Suppressor of Cytokine Signaling Proteins
  • Suppressor of Cytokine Signaling 1 Protein
  • Receptors, Interleukin-12
  • RNA, Small Interfering
  • RNA Interference
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice