The pH-Sensitive Fusogenic 3-Methyl-Glutarylated Hyperbranched Poly(Glycidol)-Conjugated Liposome Induces Antigen-Specific Cellular and Humoral Immunity

被引:13
|
作者
Hebishima, Takehisa [1 ,4 ]
Yuba, Eiji [3 ]
Kono, Kenji [3 ]
Takeshima, Shin-nosuke [1 ]
Ito, Yoshihiro [2 ]
Aida, Yoko [1 ]
机构
[1] RIKEN, Viral Infect Dis Unit, Wako, Saitama, Japan
[2] RIKEN, Nano Med Engn Lab, Wako, Saitama, Japan
[3] Osaka Prefecture Univ, Dept Appl Chem, Grad Sch Engn, Naka Ku, Sakai, Osaka 591, Japan
[4] Univ Tokyo, Grad Sch Agr & Life Sci, Bunkyo Ku, Tokyo, Japan
关键词
VIROSOME-MEDIATED DELIVERY; DENDRITIC CELLS; INTRACELLULAR TRAFFICKING; PROTECTIVE IMMUNITY; PROTEIN ANTIGENS; BALB/C MICE; VACCINE; INDUCTION; DERIVATIVES; RESPONSES;
D O I
10.1128/CVI.00273-12
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We examined the ability of a novel liposome, surface modified by 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG), to enhance antigen-specific immunity in vitro and in vivo and to function as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) encapsulated in MGlu-HPG-modified liposomes more effectively than free OVA or OVA encapsulated in unmodified liposomes. Immunization of mice with OVA-containing MGlu-HPG-modified liposomes induced antigen-specific splenocyte proliferation and production of gamma interferon (IFN-gamma) more strongly than did immunization with free OVA or OVA encapsulated in unmodified liposomes. The immune responses induced by OVA encapsulated in MGlu-HPG-modified liposomes were significantly suppressed by addition of anti-major histocompatibility complex (MHC) class I and class II monoclonal antibodies, indicating the involvement of antigen presentation via MHC class I and II. Furthermore, delayed-type hypersensitivity responses and OVA-specific antibodies were induced more effectively in mice immunized with OVA encapsulated by MGlu-HPG-modified liposomes than with unencapsulated OVA or OVA encapsulated in unmodified liposomes. These results suggested that MGlu-HPG-modified liposomes effectively induced both cell-mediated and humoral immune responses. Collectively, this study is the first to demonstrate the induction of both cell-mediated and humoral immune responses in vivo by MGlu-HPG-modified liposomes.
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页码:1492 / 1498
页数:7
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