Effective CD8+ T cell priming and tumor protection by enterotoxin B subunit-conjugated peptides targeted to dendritic cells

In our previous studies we have shown that bacterial enterotoxin B subunits are effective vehicles to deliver antigen into the MHC class I processing route. Here we have used the non-toxic Escherichia coli heat labile enterotoxin B subunit (EtxB) conjugated to OVA peptide (EtxB–peptide) to address the impact on induction of specific CD8+ T cells in vivo. Although incubation of DCs with these EtxB–peptide conjugates as such did not induce DC maturation in vitro MHC class I antigen presentation was much more efficient as compared to peptide alone. Antigen presentation was further enhanced upon DC maturation with the TLR-4 ligand LPS. Injection of matured DCs incubated with EtxB–peptide conjugates lead to strong induction of OVA-specific CD8+ T lymphocytes and fully prevented the outgrowth of lethal B16 melanoma in wild type mice. Our data demonstrate that bacterial non-toxic B subunit–peptide conjugates are potent vaccine vehicles for induction of protective CD8+ T cell responses.