Published ahead of print on June 7, 2007, doi:10.1164/rccm.200610-1405OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200610-1405OC
Novel Recombinant Interleukin-13 Peptide-based Vaccine Reduces Airway Allergic Inflammatory Responses in Mice1 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; 2 Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada; 3 Department of Immunology, 4 Department of Medical Microbiology, and 5 Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada Correspondence and requests for reprints should be addressed to Dr. Zhikang Peng, Department of Pediatrics and Child Health, University of Manitoba, 532-715 McDermot Avenue, Winnipeg, MB, R3E 3P4 Canada. 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 airway allergic 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 a persistent effect basis and to evaluate its in vivo effects using a murine model. 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 intraperitoneal sensitization and intranasal challenge with ovalbumin. Control animals received carrier or saline in place of vaccine. Measurements and Main Results: The vaccine presented as virus-like particles and induced sustained and high titered 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. Conclusions: 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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