title: Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch.
abstract: The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC]) adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators.
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Yen-Ku
authors.initials: YK
authors.lastname: Liu
authors.forename: Pei-Juin
authors.initials: PJ
authors.lastname: He
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Lin
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chiu
authors.forename: Chang-Jer
authors.initials: CJ
authors.lastname: Wu
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liao
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018834:Chaperonin 60 / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018834:Chaperonin 60; D016207:Cytokines; D007074:Immunoglobulin G; D008081:Liposomes; D008562:Membrane Glycoproteins; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine