title: Induction of a Th1 immune response and suppression of IgE via immunotherapy with a recombinant hybrid molecule encapsulated in liposome-protamine-DNA nanoparticles in a model of experimental allergy.
abstract: Liposome-protamine-DNA nanoparticles (LPD) are safe, effective, and non-toxic adjuvants that induce Th1-like immune responses. We hypothesized that encapsulation of allergens into liposomes could be an appropriate option for immunotherapy. The present study evaluated the immunotherapeutic potential of a recombinant hybrid molecule (rHM) encapsulated in LPD nanoparticles in a murine model of Chenopodium album allergy. BALB/c mice were sensitized with the allergen in alum, and the immunotherapy procedure was performed by subcutaneous injections of LPD-rHM, rHM, or empty LPD at weekly intervals. Sensitized mice developed a Th2-biased immune response characterized by strong specific IgG1 and IgE production, IL-4, and the transcription factor GATA3 in spleen cell cultures. Treatment with the LPD-rHM resulted in a reduction in IgE and a marked increase in IgG2a. The LPD-rHM induced allergen-specific responses with relatively high interferon-gamma production, as well as expression of the transcription factor T-bet in stimulated splenocytes. In addition, lymphoproliferative responses were higher in the LPD-rHM-treated mice than in the other groups. Removal of the nanoparticles from the rHM resulted in a decrease in the allergen's immunogenicity. These results indicate that the rHM complexed with LPD nanoparticles has a marked suppressive effect on the allergic response and caused a shift toward a Th1 pathway.
authors.affiliation: Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran, nourihr851@gmail.com.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Nouri
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Varasteh
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
authors.forename: Janet M
authors.initials: JM
authors.lastname: Davies
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Sankian
mesh_terms: D000818:Animals; D027463:Chenopodium album / Q000276:immunology*; D004247:DNA / Q000494:pharmacology*; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D008081:Liposomes / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules; D011479:Protamines / Q000494:pharmacology*; D011897:Random Allocation; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007074:Immunoglobulin G; D008081:Liposomes; D053769:Nanocapsules; D011479:Protamines; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA