The B subunit of Shiga toxin coupled to full-size antigenic protein elicits humoral and cell-mediated immune responses associated with a Th1-dominant polarization

被引:56
作者
Haicheur, N
Benchetrit, F
Amessou, M
Leclerc, C
Falguières, T
Fayolle, C
Bismuth, E
Fridman, WH
Johannes, L
Tartour, E
机构
[1] Univ Paris 06, Hop Europeen Georges Pompidou, AP HP Unite Immunol Biol, INSERM,U255, F-75015 Paris, France
[2] Inst Pasteur, Traff & Signaling Lab, CNRS, UMR144, F-75248 Paris 05, France
[3] Inst Pasteur, INSERM E0352, Unite Biol Regulat Immunitaires, F-75015 Paris, France
关键词
antigen presentation/processing; cell trafficking; cytotoxic T lymphocyte; vaccination;
D O I
10.1093/intimm/dxg118
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A number of studies in animal models and humans have shown that both humoral and cell-mediated immune responses play an important role in the control of viral infection and tumor development. In most cases, vaccination with non-vectorized peptides or proteins induces low antibody responses and fails to elicit specific cytotoxic T lymphocytes (CTL). In order to make vaccination more efficient, we chemically coupled the non-toxic B subunit of Shiga toxin (STxB) to a full-size antigenic model protein, ovalbumin (OVA), yielding STxB-OVA. We found that STxB-OVA delivers OVA-derived peptides into both the MHC class I- and II-restricted presentation pathways in mouse dendritic cells. Accordingly, the study of STxB trafficking in these cells revealed that, after internalization, a fraction of STxB followed the retrograde transport pathway to the endoplasmic reticulum, while another fraction was targeted to late endosomes/lysosomes. Vaccination of mice with STxB-OVA primed a specific anti-OVA CTL response without the use of adjuvants. Splenocytes and, particularly, CD4(+) T cells from mice immunized with STxB-OVA also produced higher amounts of the T(h)1 cytokine IFNr-gamma and IgG2a-type antibodies than mice immunized with non-vectorized ovalbumin. In conclusion, this study identifies a unique non-live vaccine delivery system for polyepitopic antigens that elicits antigen-specific CTL, a humoral immune response and a T(h)1-type polarization without the use of adjuvant.
引用
收藏
页码:1161 / 1171
页数:11
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