title: Polymer blend particles with defined compositions for targeting antigen to both class I and II antigen presentation pathways.
abstract: Defense against many persistent and difficult-to-treat diseases requires a combination of humoral, CD4(+) , and CD8(+) T-cell responses, which necessitates targeting antigens to both class I and II antigen presentation pathways. In this study, polymer blend particles are developed by mixing two functionally unique polymers, poly(lactide-co-glycolide) (PLGA) and a pH-responsive polymer, poly(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate) (DMAEMA-co-PAA-co-BMA). Polymer blend particles are shown to enable the delivery of antigens into both class I and II antigen presentation pathways in vitro. Increasing the ratio of the pH-responsive polymer in blend particles increases the degree of class I antigen presentation, while maintaining high levels of class II antigen presentation. In a mouse model, it is demonstrated that a significantly higher and sustained level of CD4(+) and CD8(+) T-cell responses, and comparable antibody responses, are elicited with polymer blend particles than PLGA particles and a conventional vaccine, Alum. The polymer blend particles offer a potential vaccine delivery platform to generate a combination of humoral and cell-mediated immune responses that insure robust and long-lasting immunity against many infectious diseases and cancers.
authors.affiliation: University of Washington, Department of Chemical Engineering, Campus Box 351750, Seattle, WA, 98195, USA.
authors.forename: Kenny K
authors.initials: KK
authors.lastname: Tran
authors.forename: Xi
authors.initials: X
authors.lastname: Zhan
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000534:Alum Compounds; D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D042541:Intracellular Space / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000534:Alum Compounds; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011108:Polymers; C041524:aluminum sulfate
keywords: adjuvants; antigen presentation; blend polymers; cross-presentation; vaccines