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International Immunology, Vol. 15, No. 10, pp. 1161-1171, October 2003
© 2003 Japanese Society for Immunology

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

Nacilla Haicheur1, Fabrice Benchetrit1, Mohamed Amessou2, Claude Leclerc3, Thomas Falguières2, Catherine Fayolle3, Emmanuelle Bismuth2, Wolf H. Fridman1, Ludger Johannes2 and Eric Tartour1

1 INSERM U255, Université Pierre et Marie Curie, AP-HP Unité d’Immunologie Biologique, Hopital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France 2 UMR144 Institut Curie/CNRS, Traffic and Signaling Laboratory, 75248 Paris Cedex 05, France 3 Unité de Biologie des Régulations Immunitaires, INSERM E0352, Institut Pasteur, 75015 Paris, France

The first two authors contributed equally to this work; the last two authors are the principal investigators
Correspondence to: E. Tartour; E-mail: Eric.TARTOUR{at}hop.egp.ap-hop-paris.fr
Transmitting editor: I. Pecht

A number of studies in animal models and humans have shown that both humoral andcell-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 Th1 cytokine IFN-{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 Th1-type polarization without the use of adjuvant.

Keywords: antigen presentation/processing, cell trafficking, cytotoxic T lymphocyte, vaccination


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