A plant-based allergy vaccine suppresses experimental asthma via an IFN-gamma and CD4+CD45RBlow T cell-dependent mechanism.
Allergic asthma is currently considered a chronic airway inflammatory disorder associated with the presence of activated CD4(+) Th2-type lymphocytes, eosinophils, and mast cells. Interestingly, therapeutic strategies based on immune deviation and suppression have been shown to successfully attenuate the development of the asthma phenotype. In this investigation, we have for the first time used a genetically modified (GM) plant, narrow leaf lupin (Lupinus angustifolius L.), expressing a gene for a potential allergen (sunflower seed albumin) (SSA-lupin) to examine whether a GM plant/food-based vaccine strategy can be used to suppress the development of experimental asthma. We show that oral consumption of SSA-lupin promoted the induction of an Ag-specific IgG2a Ab response. Furthermore, we demonstrate that the plant-based vaccine attenuated the induction of delayed-type hypersensitivity responses and pathological features of experimental asthma (mucus hypersecretion, eosinophilic inflammation, and enhanced bronchial reactivity (airways hyperreactivity). The suppression of experimental asthma by SSA-lupin was associated with the production of CD4(+) T cell-derived IFN-gamma and IL-10. Furthermore, we show that the specific inhibition of experimental asthma was mediated via CD4(+)CD45RB(low) regulatory T cells and IFN-gamma. Thus, our data demonstrate that a GM plant-based vaccine can promote a protective immune response and attenuate experimental asthma, suggesting that plant-based vaccines may be potentially therapeutic for the protection against allergic diseases.
Smart
Vanessa
V
Allergy and Inflammation Research Group, Division of Molecular Bioscience, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Foster
Paul S
PS
Rothenberg
Marc E
ME
Higgins
T J V
TJ
Hogan
S P
SP
D055516:2S Albumins, Plant; D000485:Allergens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006368:Helianthus / Q000235:genetics / Q000276:immunology*; D007115:Immunization Schedule; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D031297:Lupinus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D030821:Plants, Genetically Modified / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D012639:Seeds / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; D007166:Immunosuppressive Agents; D010940:Plant Proteins; D019444:Vaccines, DNA; C067568:methionine-rich 2S protein, Helianthus; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens