Original Articles: Mechanisms of AllergyIFN-γ and IL-12 plasmid DNAs as vaccine adjuvant in a murine model of grass allergy☆,☆☆
Section snippets
Animals
Female B6D2F1 mice, 6 to 8 weeks old, from Jackson Laboratory (Bar Harbor, Me) were maintained in pathogen-free conditions at the animal center at the James A. Haley Veterans Hospital. All procedures were reviewed and approved by the committee on animal research at the James A. Haley VA Medical Center and the University of South Florida College of Medicine.
Vaccination protocol
Four groups of naive mice (n = 12) were intramuscularly vaccinated 3 times at intervals of 2 days, each in its right quadriceps muscle, with
Plasmid constructs and expression of IL-12 and IFN-γ
The 2 subunits of murine IL-12, p35 and p40, were cloned into the same pcDNA3.1 vector. The cloning strategy was such that each subunit was under the transcriptional control of an individual CMV immediate-early promoter and also had its own BGH poly A sequences derived from the vector pcDNA3.1. Mice given pIFN-γ or pIL-12 exhibited expression of the IFN-γ or IL-12 p40 subunit, respectively, in their muscle, as observed by immunohistochemical staining of the muscle tissues (Fig 1, A , a and c ).
Discussion
Previously, it was shown in a mouse model that effective parenteral vaccination of mice with grass allergens required subcutaneous injection of a high dose (250 μg to 1 mg per mouse) of allergens.14 By corollary, an even higher dose of allergen mixture would be required to induce an effective immune deviation from an allergic response. The results of this study demonstrate that in a mouse, a substantially lower dosage (50 μg) of allergens, when administered along with a pDNA cytokine(s)
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Recombinant plasmids containing CpG with porcine host defense peptides (PR-39/pBD-1) modulates the innate and adaptive intestinal immune responses (including maternal-derived) in piglets
2019, International ImmunopharmacologyCitation Excerpt :To address this deficiency, scientists used plasmids directly as vaccine adjuvants [26]. Mukesh Kumar et al. (2001) constructed a recombinant plasmid containing the IFN-γ and IL-12 genes, which proved to be effective as a vaccine adjuvant to improve human allergen immunity [27]. A similar finding was reported by Krieg AM et al. that the presence of a CpG motif provided the necessary immunoadjuvant signal for DNA vaccination [28].
Effects of a DNA vaccine in an animal model of Alternaria alternata sensitivity
2009, Revista Iberoamericana de MicologiaVaccination to treat noninfectious diseases: Surveying the opportunities
2006, Immunopotentiators in Modern VaccinesVaccination to treat noninfectious diseases: Surveying the opportunities
2005, Immunopotentiators in Modern VaccinesRationale for new treatments aimed at IgE immunomodulation
2004, Annals of Allergy, Asthma and ImmunologyAllergen rush immunotherapy increases interleukin (IL)-12 production and IL-12 receptor β2 chain expression in patients with allergic asthma
2004, Cellular ImmunologyCitation Excerpt :IL-12 is an important cytokine for the differentiation of naive T cells to Th1 cells. Administration of IL-12 to mice by inhalation or gene delivery into epithelial cells inhibits Th2 cytokine production, eosinophilic airway inflammation, and airway hyperresponsiveness in the mouse model of asthma [22–26]. In patients with allergic asthma, expression of IL-12 p35 mRNA is decreased in bronchial biopsy specimens [10].
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Supported by an American Lung Association of Florida Career Development Award to S.S.M. and partly by grants from the VA Merit Review Award and the American Heart Association, Florida, Affiliate Award to S.S.M. Generous support was also given by the Joy McCann Culverhouse endowment to the Division of Allergy and Immunology.
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Reprint requests: Shyam S. Mohapatra, PhD, Department of Internal Medicine, Division of Allergy and Immunology—Joy McCann Culverhouse Airway Disease Center, University of South Florida and VA Hospital, 12901 Bruce B Downs Blvd, Tampa, FL 33612.