Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model

Vaccine. 2015 Aug 20;33(35):4313-20. doi: 10.1016/j.vaccine.2015.03.086. Epub 2015 Apr 14.

Abstract

Identifying new molecular adjuvants that elicit effective vaccine-induced CD8(+) T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular adjuvant IL-33 during vaccination enhanced the magnitude and function of antigen (Ag)-specific CD8(+) T cells against a model Ag, LCMV NP target protein. These enhanced responses were characterized by higher frequencies of Ag-specific, polyfunctional CD8(+) T cells exhibiting cytotoxic characteristics. Importantly, these cells were capable of robust expansion upon Ag-specific restimulation in vivo and conferred remarkable protection against a high dose lethal LCMV challenge. In addition, we demonstrate the ability of IL-33 to amplifying the frequency of Ag-specific KLRG1(+) effector CD8(+) T cells. These data show that IL-33 is a promising immunoadjuvant at improving T cell immunity in a vaccine setting and suggest further development and understanding of this molecular adjuvant for strategies against many obstinate infectious diseases and cancer.

Keywords: Adjuvants; CD8 T cells; DNA vaccines; HIV; IL-33; LCMV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology
  • Adjuvants, Immunologic*
  • Animals
  • Arenaviridae Infections / prevention & control
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Immunity, Cellular
  • Immunologic Memory
  • Interleukin-33 / genetics
  • Interleukin-33 / immunology*
  • Lymphocytic choriomeningitis virus / genetics
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice, Inbred C57BL
  • Vaccines, DNA / immunology*

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Interleukin-33
  • Vaccines, DNA