title: Polycation-decorated PLA microspheres induce robust immune responses via commonly used parenteral administration routes.
abstract: Recombinant viral subunit-based vaccines have gained increasing attention due to their enhanced safety over the classic live-attenuated or inactivated vaccines. The low immunogenicity of the subunit antigen alone, however, requires the addition of an adjuvant to induce immunity. Particulate-based delivery systems have great potential for developing new vaccine adjuvants, compared to traditional aluminum-based saline adjuvants. The physicochemical properties of particulate vaccines have been extensively investigated; however, few studies have focused on how the administration route of various adjuvant-antigen combinations impacts the efficacy of the immune response. Here, for the first time, the viral Hepatitis B surface antigen (HBsAg) was combined with aluminum-based or cationic-microsphere (MP) based adjuvants to investigate the characteristics of immune responses elicited after immunization via the subcutaneous, intramuscular, or intraperitoneal routes respectively. In vitro, the MP-based vaccine significantly increased dendritic cell (DC) activation with up-regulated CD40 and CD80 expression and IL-12 production compared to alum-based vaccine. After immunization, both MP and alum-based vaccines produced increased IgG titers in mice. The administration route of these vaccines did influenced immune responses. The MP-based vaccine delivered via the intramuscular route yielded the highest levels of the IgG2a isotype. The alum-based vaccine, delivered via the same route, produced an IgG1-dominated humoral immune response. Moreover, subcutaneous and intramuscular immunizations with MP-based vaccine augmented Granzyme B, Th1-type cytokines (IL-2, IL-12, and IFN-γ), and Th2 cytokine IL-4 secretions. These results demonstrate that MP-based vaccines have the capacity to induce higher cellular and humoral immune response especially via an intramuscular administration route than an alum-based vaccine.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Jilei
authors.initials: J
authors.lastname: Jia
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D019013:CD40 Antigens; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011091:Polyesters; D011108:Polymers; D018664:Interleukin-12; D019344:Lactic Acid; C033616:poly(lactide); D000536:Aluminum Hydroxide