title: Effects of a DNA vaccine in an animal model of Alternaria alternata sensitivity.
abstract: Sensitivity to the fungus Alternaria is associated with asthma persistence and severity. Current therapeutic options for treating Alternaria-induced airway inflammation are limited. In this study, Brown Norway rats are used to study the effectiveness of a DNA-based vaccine delivered to the airway in attenuating the response to a major Alternaria allergen, rAlt a 2. Compared to untreated sensitized animals, or animals receiving an "out-of-frame" DNA-based vaccine, animals treated with "in-frame" DNA vaccine showed an attenuation in specific IgE antibody titers to rAlt a 2, an increase in IgG(2b) (a Th1 response), a reduction in spontaneous IL-13 release by peribronchial lymph node cell suspensions, and an attenuation in the decrease in total lung capacity 72 h post-allergen challenge. Further, histopathologic examination of the lung tissues revealed reduced pulmonary inflammation post-allergen challenge in the DNA-vaccine-treated compared to sensitized, untreated animals. We conclude that a DNA-based vaccine delivered to the airway significantly influences the immunologic, pulmonary physiologic, and histological alterations induced by challenge with a major Alternaria allergen, rAlt a 2, in sensitized animals.
authors.affiliation: Allergy Section, William S. Middleton Memorial VA Hospital, Madison, WI, USA; Department of Medicine, University of Wisconsin, Madison, WI, USA. hxs@medicine.wisc.edu
authors.forename: Hiram
authors.initials: H
authors.lastname: Sánchez
authors.forename: Robert K
authors.initials: RK
authors.lastname: Bush
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: Amjad
authors.initials: A
authors.lastname: Tuffaha
authors.forename: Louis A
authors.initials: LA
authors.lastname: Rosenthal
authors.forename: Lynette
authors.initials: L
authors.lastname: Phillips
mesh_terms: D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000528:Alternaria / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000235:genetics / Q000276:immunology*; D004271:DNA, Fungal / Q000008:administration & dosage / Q000276:immunology*; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007327:Insufflation; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014109:Total Lung Capacity; D014132:Trachea; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014797:Vital Capacity
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D004271:DNA, Fungal; D005656:Fungal Proteins; D007074:Immunoglobulin G; D018793:Interleukin-13; C121953:R ALT A 2 protein, Alternaria alternata; D019444:Vaccines, DNA; D007073:Immunoglobulin E; D007371:Interferon-gamma