pcDNA-IL-12 vaccination blocks eosinophilic inflammation but not airway hyperresponsiveness following murine Toxocara canis infection

Vaccine. 2008 Jan 17;26(3):305-15. doi: 10.1016/j.vaccine.2007.11.023. Epub 2007 Nov 29.

Abstract

We have investigated the effect of pcDNA3-CpG and pcDNA-IL-12, delivered by intradermal gene gun administration, on the blood/lung eosinophilia, airway hyperresponsiveness as well as the immune response in a murine model of toxocariasis. Our results demonstrated that pcDNA-IL-12 but not pcDNA3-CpG vaccination led to a persistent lower blood/bronchoalveolar eosinophilia following Toxocara canis infection, as pcDNA3-CpG led only to an early transient blockage of eosinophil transmigration into bronchoalveolar fluid following T. canis infection. Prominent Type-1 immune response was pointed out as the hallmark of T. canis infection following pcDNA-IL-12 vaccination. Outstanding IFN-gamma/IL-4 ratio besides low levels of IgG1 with subsequent high IgG2a/IgG1 ratio further characterized a Type-1 polarized immunological profile in pcDNA-IL-12-vaccinated animals. Nevertheless, only pcDNA3-CpG was able to prevent airway hyperresponsiveness induced by T. canis infection. The persistent airway hyperresponsiveness observed in pcDNA-IL-12-vaccinated animals demonstrated that the airway constriction involved other immunological mediator than those blocked by pcDNA-IL-12. Together, these data indicated that pcDNA-IL-12 and pcDNA3-CpG vaccines have distinct therapeutic benefits regarding the eosinophilic inflammation/airway hyperresponsiveness triggered by T. canis infection, suggesting their possible use in further combined therapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biolistics
  • Bronchial Hyperreactivity / prevention & control*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • CpG Islands* / genetics
  • CpG Islands* / immunology
  • Dogs
  • Female
  • Interleukin-12* / administration & dosage
  • Interleukin-12* / genetics
  • Interleukin-12* / immunology
  • Lung / cytology
  • Lung / immunology
  • Mice
  • Mice, Inbred BALB C
  • Plasmids / genetics*
  • Pulmonary Eosinophilia / prevention & control*
  • Toxocara canis
  • Toxocariasis / complications*
  • Toxocariasis / immunology
  • Toxocariasis / parasitology
  • Treatment Outcome
  • Vaccination
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology

Substances

  • Vaccines, DNA
  • Interleukin-12