Published ahead of print on June 7, 2007, doi:10.1164/rccm.200610-1405OC Am. J. Respir. Crit. Care Med., Volume 176, Number 5, September 2007, 439-445 A more recent version of this article appeared on September 1, 2007
Submitted on October 3, 2006 Novel Recombinant IL-13 Peptide-based Vaccine Reduces Airway Allergic Inflammatory Responses in MiceYanbing Ma1,1 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada, 2 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada, 3 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada, 4 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada, 5 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada, 6 Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada, 7 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada, 8 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada * To whom correspondence should be addressed. E-mail: zpeng{at}ms.umanitoba.ca.
Rationale: Interleukin (IL)-13 plays a pivotal role in the pathogenesis of allergic asthma. Passive administration of its monoclonal antibody or soluble receptor to block overproduced IL-13 has been proven to be effective in controlling asthmatic responses in animal models, but these approaches have disadvantages of short half-lives, high costs and possible adverse effects. Objectives: We sought to develop a novel therapeutic strategy through constructing an IL-13 peptide-based vaccine for blocking IL-13 on persistent effect basis and to evaluate its in vivo effects using a murine model of asthma. Methods: To break self-tolerance, truncated hepatitis B core antigen was used as a carrier. Vaccine was prepared by inserting a peptide derived from the receptor binding site of mouse IL-13 into the immunodominant epitope region of the carrier using gene recombination methods. Mice received vaccine subcutaneously three times, and then subjected to introperitoneal sensitization and intranasal challenge with ovalbumin. Control animals received carrier or saline in place of vaccine. Results: The vaccine presented as virus-like particles and induced sustained and high titred IL-13 specific IgG without the use of conventional adjuvant. Vaccination significantly suppressed ovalbumin-induced inflammatory cell number, and IL-13 and IL-5 levels in bronchoalveolar lavage fluids. Serum total and ovalbumin-specific IgE were also significantly inhibited. Moreover, allergen-induced goblet cell hyperplasia, lung tissue inflammatory cell infiltration, and pulmonary hyperresponsiveness to inhaled methacholine were significantly suppressed in vaccinated mice. Conclusion: Our data indicate that IL-13 peptide-based vaccines could be an effective therapeutic approach in the treatment of asthma. Key words: interleukin-13, vaccine, airway allergic responses, Th2 cytokine, asthma
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