Transient IL-10 receptor blockade can enhance CD8(+) T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen

Hum Vaccin Immunother. 2015;11(4):1030-5. doi: 10.1080/21645515.2015.1009809.

Abstract

Viral vector vaccines designed to elicit CD8(+) T cells in non-human primates exert potent control of immunodeficiency virus infections; however, similar approaches have been unsuccessful in humans. Adenoviral vectors elicit potent T cell responses but also induce production of immunosuppressive interleukin-10 (IL-10), which can limit the expansion of T cell responses. We investigated whether inhibiting IL-10 signaling prior to immunization with a candidate adenovirus vectored-HIV-1 vaccine, ChAdV63.HIVconsv, could modulate innate and adaptive immune responses in BALB/c mice. Transient IL-10 receptor blockade led to a modest but significant increase in the total magnitude CD8(+) T cell response to HIVconsv, but did not affect T cell responses to immunodominant epitopes. Anti-IL-10R-treated animals also exhibited greater expression of CD86 on CD11c(+) dendritic cells. Our data support further investigation and optimization of IL-10 blocking strategies to improve the immunogenicity of vaccines based on replication-defective adenoviruses.

Keywords: HIV-1; T cells; interleukin-10; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines
  • Adenoviruses, Simian / genetics*
  • Animals
  • B7-2 Antigen / metabolism
  • CD11c Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Enzyme-Linked Immunospot Assay
  • Female
  • Genetic Vectors / genetics*
  • HIV Antibodies
  • HIV Infections
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-10 / antagonists & inhibitors*

Substances

  • AIDS Vaccines
  • B7-2 Antigen
  • CD11c Antigen
  • HIV Antibodies
  • Receptors, Interleukin-10