Exotoxin conjugates and their therapeutic uses

Patent Summary

A recombinant vaccine, composed of an in vitro protein fusion between a bacterial toxin and a protein to raise an immune response, is described. This single protein can carry several domains which will allow the correct processing and presentation to T lymphocytes and thus elicit a strong immune response.

The structure of the Pseudomonas exotoxin A contains several domains. One of these enables the toxin to be internalised into cells through endocytosis via receptors on the cell surface then translocate out of the resultant endosome into the cellular compartment where endogenous proteins are processed for presentation by Class I MHC proteins. The ADP-ribosylation domain of the toxin is deleted to prevent it killing the cells and the protein coding region of the protein of interest is fused to the translocation domains. In this example the protein is fused to residues 57 to 68 of the matrix protein of influenza A, an epitope known to bind to MHC HLA2. Other antigenic epitopes from HIV, papilloma virus, cytomegalovirus, Epstein-Barr virus, rotavirus, respiratory syncytial virus, tumours and parasites can be presented to T cells in this way.