Novel protein toxin-based strategy for development of cytotoxic T lymphocyte vaccines

Specific activation of CD8+ cytotoxic T lymphocytes (CTL) is crucial to elicit immunity against intracellular pathogens including viruses, bacteria and protozoa. CTLs recognize mainly intracellularly processed peptides of pathogen origin associated with major histocompatibility complex class I molecules (MHC class I) at the cell surface of infected cells. It implicates the way how to induce specific CTL response and develop an efficient vaccine against intracellular pathogens. Therefore, the general strategy is to mimic the infection by introducing the target antigen into the cytosol of host cells in vivo. Several approaches have been proposed so far, including self replicating vectors, adjuvants and liposomes. However, none of them are ready for practical use. Recently, it has been shown that a number of protein toxins can be used to carry passenger proteins across cellular membranes into the cytosol. This suggested new possibilities for how to deliver a protein antigen into the cytosol for intracellular processing and presentation by MHC class I and to develop CTL vaccines. Here the use of protein toxins as translocation vehicles for delivery of antigen peptides into the cytosol is discussed. Experimental data already obtained demonstrating in vivo elicited immunity by the toxin systems are reviewed and considered.