title: Immune responses to vaccines delivered by encapsulation into and/or adsorption onto cationic lipid-PLGA hybrid nanoparticles.
abstract: In this study, we used cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles as antigen delivery carriers to investigate how antigen-loading methods affect antigen exposure to the immune system and evaluated the resulting antigen-specific immune responses. We formulated three classes of antigen adsorbed and/or encapsulated cationic lipid-PLGA hybrid nanoparticles; we designated antigen-adsorbed (out), antigen-encapsulated (in), and antigen-adsorbed/encapsulated (both) nanoparticles. Our results demonstrate significantly more efficient lysosomal escape and cross-presentation of antigen from dendritic cells (DCs) that were exposed to "both" and "in" nanoparticles. In vivo experiments further revealed that "both" nanoparticles significantly more effectively provided not only adequate initial antigen exposure but also long-term antigen persistence at the injection site. Data from flow cytometry and ELISA analyses demonstrated elevated in vivo immune responses from mice that were immunized with nanoparticles-delivered OVA when compared with free OVA. In addition, "in" and "both" nanoparticles elicited significantly higher antigen-specific immune response than "out" nanoparticles and free OVA. These results suggest that the location of antigen entrapment is an important factor in modulating the immune responses of antigens delivered by nanoparticles. Overall, we propose here a promising approach for the future design of vaccines using cationic lipid-PLGA nanoparticles.
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Lanxia
authors.initials: L
authors.lastname: Liu
authors.affiliation: Tianjin Central Gynecology and Obstetrics Hospital, Tianjin 300100, China.
authors.forename: Pingchuan
authors.initials: P
authors.lastname: Ma
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Hongfan
authors.initials: H
authors.lastname: Sun
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China; Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Cunxian
authors.initials: C
authors.lastname: Song
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Xigang
authors.initials: X
authors.lastname: Leng
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China. Electronic address: bmemgl@126.com.
authors.forename: Guilei
authors.initials: G
authors.lastname: Ma
mesh_terms: D000327:Adsorption; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051940:B7-2 Antigen / Q000276:immunology; D001692:Biological Transport; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013154:Spleen / Q000166:cytology; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000941:Antigens; D051940:B7-2 Antigen; D007074:Immunoglobulin G; D014612:Vaccines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015847:Interleukin-4; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; D010047:Ovalbumin; D002784:Cholesterol
keywords: Adjuvant; Adsorption; Cationic-lipid PLGA hybrid nanoparticles; Encapsulation; Immune response; Vaccine