Vaccination with allergen-IL-18 fusion DNA protects against, and reverses established, airway hyperreactivity in a murine asthma model.
Vaccination with naked DNA encoding a specific allergen has been shown previously to prevent, but not reverse, the development of allergen-induced airway hyperresponsiveness (AHR). To enhance the effectiveness of DNA vaccine therapies and make possible the treatment of established AHR, we developed a DNA vaccination plasmid containing OVA cDNA fused to IL-18 cDNA. Vaccination of naive mice either with this fusion DNA construct or with an OVA cDNA-containing plasmid protected the mice from the subsequent induction of AHR. Protection from AHR correlated with increased IFN-gamma production and reduced OVA-specific IgE production. The protection appeared to be mediated by IFN-gamma and CD8(+) cells because treatment of mice with neutralizing anti-IFN-gamma mAb or with depleting anti-CD8 mAb abolished the protective effect. Moreover, vaccination of mice with preexisting AHR with the OVA-IL-18 fusion DNA, but not with the OVA cDNA plasmid, reversed established AHR, reduced allergen-specific IL-4, and increased allergen-specific IFN-gamma production. Thus, combining IL-18 cDNA with OVA cDNA resulted in a vaccine construct that protected against the development of AHR, and that was unique among cDNA constructs in its capacity to reverse established AHR.
Maecker
H T
HT
Division of Oncology, Department of Medicine, and the Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94305, USA.
Hansen
G
G
Walter
D M
DM
DeKruyff
R H
RH
Levy
S
S
Umetsu
D T
DT
D000485:Allergens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
D000485:Allergens; D019138:Antibodies, Blocking; D016207:Cytokines; D000939:Epitopes; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin