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.
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 T(h)1 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 T(h)1-type polarization without the use of adjuvant.
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000502:physiology; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D051379:Mice; D009097:Multienzyme Complexes / Q000502:physiology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D022621:Shiga Toxin / Q000276:immunology / Q000378:metabolism; D022603:Shiga Toxins / Q000235:genetics*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D009097:Multienzyme Complexes; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D022603:Shiga Toxins; C077239:stxB toxin; D022621:Shiga Toxin; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex