Enhancement of IL-10 bioactivity using an IL-10 peptide-based vaccine exacerbates Leishmania major infection and improves airway inflammation in mice

Vaccine. 2010 Feb 17;28(7):1838-46. doi: 10.1016/j.vaccine.2009.11.081. Epub 2009 Dec 14.

Abstract

IL-10 is a regulatory cytokine that plays important roles in promoting disease progression in cutaneous leishmaniasis and suppressing allergic responses in asthma. We sought to develop an IL-10 peptide-based vaccine for the control of IL-10-related diseases. To break self-tolerance, hepatitis B core antigen (HBcAg) was used as a carrier. The vaccine was prepared by inserting a peptide derived from mouse IL-10 into the carrier using gene recombination methods. This vaccine presented as virus-like particles, bound to polyclonal anti-IL-10 antibodies, and induced high titers of IL-10-specific IgG. The in vivo effects of the vaccine were investigated in a murine model of cutaneous leishmaniasis. Unexpectedly, vaccinated mice developed larger cutaneous lesions, harbored significantly more parasites, and cells from lymph nodes produced higher amounts of parasite-specific IL-4, IL-10 and IFN-gamma in cultures. Further in vitro studies showed that serum IL-10-specific IgG from vaccinated mice significantly enhanced IL-10 bioactivity dose-dependently. This enhancing effect was confirmed in OVA-induced asthmatic mice. Vaccinated mice exhibited a significant decrease in airway eosinophils, lung inflammation, goblet hyperplasia, and levels of serum OVA-specific IgE, compared to control mice. We concluded that the IL-10 vaccine enhances the bioactivity of IL-10 in vitro and in vivo, providing a potential therapeutic approach in diseases associated with insufficient IL-10 production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology
  • Asthma / therapy*
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Disease Progression
  • Eosinophils / immunology
  • Female
  • Hepatitis B Core Antigens / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Interleukin-10 / adverse effects*
  • Interleukin-10 / immunology*
  • Interleukin-10 / therapeutic use
  • Interleukin-4 / immunology
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Pneumonia / drug therapy
  • Pneumonia / immunology
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Vaccines, Subunit / immunology*

Substances

  • Autoantibodies
  • Hepatitis B Core Antigens
  • Immunoglobulin G
  • Recombinant Proteins
  • Vaccines, Subunit
  • Interleukin-10
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma