title: Biodegradable polylactide microspheres enhance specific immune response induced by Hepatitis B surface antigen.
abstract: Hepatitis B (HB) infection caused by Hepatitis B virus (HBV) is the most common liver disease in the world. HB vaccine, when administered in conjunction with alum adjuvants, induces Th2 immunity that confers protection against HBV. However, currently available vaccine formulations and adjuvants do not elicit adequate Th1 and CTL responses that are important for prevention of maternal transmission of the virus. Microspheres synthesized from poly (D, L-lactide-co-glycolide) (PLGA) or poly (D, L-lactide) (PLA) polymers have been considered as promising tools for in vivo delivery of antigens and drugs. Here we describe PLA microspheres synthesized by premix membrane emulsification method and their application in formulating a new microsphere based HB vaccine. To evaluate the immunogenicity of this microsphere vaccine, BALB/c mice were immunized with microsphere vaccine and a series of immunological assays were conducted. Results of Enzyme-linked ImmunoSpot (ELISPOT) assays revealed that the number of interferon-gamma (IFN-γ)-producing splenocytes and CD8(+) T cells increased significantly in the microsphere vaccine group. Microsphere vaccine group showed enhanced specific cell lysis when compared with HB surface antigen (HBsAg) only group in (51)Cr cytotoxicity assays. Moreover, microsphere vaccine elicited a comparable level of antibody production as that of HB vaccine administered with alum adjuvant. We show that phagocytosis of HBsAg by dendritic cells is more pronounced in microsphere vaccine group when compared with other control groups. These results clearly demonstrate the potential of using PLA microspheres as effective HB vaccine adjuvants for an enhanced Th1 immune response.
authors.affiliation: a Division of Hepatitis Virus Vaccine; National Institutes for Food and Drug Control; Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products; Beijing, PR China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Qiu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Liang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.forename: Wenqi
authors.initials: W
authors.lastname: An
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.forename: Hemin
authors.initials: H
authors.lastname: Li
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D063566:Biodegradable Plastics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004337:Drug Carriers / Q000008:administration & dosage*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011091:Polyesters
chemical_list: D063566:Biodegradable Plastics; D004337:Drug Carriers; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011091:Polyesters; C033616:poly(lactide); D007371:Interferon-gamma
keywords: CTL; HBsAg; IFN-γ; anti-HBs; microspheres; polylactide