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Polycation-decorated PLA microspheres induce robust immune responses via commonly used parenteral administration routes
Alternative TitleInt. Immunopharmacol.
Chen, Xiaoming1,2; Wang, Lianyan1; Liu, Qi1,2; Jia, Jilei1,2; Liu, Yuan1,2; Zhang, Weifeng1,2; Ma, Guanghui1; Su, Zhiguo1
2014-12-01
Source PublicationINTERNATIONAL IMMUNOPHARMACOLOGY
ISSN1567-5769
Volume23Issue:2Pages:592-602
AbstractRecombinant 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-gamma), 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. (C) 2014 Elsevier B.V. All rights reserved.; 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-gamma), 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. (C) 2014 Elsevier B.V. All rights reserved.
KeywordAdministration Route Cationic Microsphere Alum Antibodies Cytokines
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1016/j.intimp.2014.10.010
URL查看原文
Indexed BySCI
Language英语
WOS KeywordHEPATITIS-B-VACCINE ; CD8(+) T-CELLS ; DENDRITIC CELLS ; DELIVERY-SYSTEMS ; ANTIGEN-DELIVERY ; ANTIBODY-RESPONSE ; CUTTING EDGE ; DNA VACCINE ; NANOPARTICLES ; ADJUVANT
WOS Research AreaImmunology ; Pharmacology & Pharmacy
WOS SubjectImmunology ; Pharmacology & Pharmacy
WOS IDWOS:000346954000031
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Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/11712
Collection研究所(批量导入)
Affiliation1.Chinese Acad Sci, Inst Proc Engn, PLA Key Lab Biopharmaceut Prod & Formulat Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Chinese Acad Sci, Graduated Univ, Beijing 100049, Peoples R China
Recommended Citation
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Chen, Xiaoming,Wang, Lianyan,Liu, Qi,et al. Polycation-decorated PLA microspheres induce robust immune responses via commonly used parenteral administration routes[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2014,23(2):592-602.
APA Chen, Xiaoming.,Wang, Lianyan.,Liu, Qi.,Jia, Jilei.,Liu, Yuan.,...&Su, Zhiguo.(2014).Polycation-decorated PLA microspheres induce robust immune responses via commonly used parenteral administration routes.INTERNATIONAL IMMUNOPHARMACOLOGY,23(2),592-602.
MLA Chen, Xiaoming,et al."Polycation-decorated PLA microspheres induce robust immune responses via commonly used parenteral administration routes".INTERNATIONAL IMMUNOPHARMACOLOGY 23.2(2014):592-602.
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