The use of signal peptide domains as vaccine candidates


Signal peptide (SP) domains have a common motif but also sequence specific features. This knowledge was mainly ignored by immunologists who considered SP as generic, short-lived, targeting sequences. Consequently, while SPderived MHC class I, class II and HLA-E epitopes have been isolated, their use as antigen-specific vaccine candidates (VCs) was mostly neglected. Recently we demonstrated the rational of selecting entire SP domains as multi-epitope long peptide VCs based on their high T and B-cell epitope densities. This review summarizes preclinical and clinical results demonstrating the various advantages of human SP domain VCs derived from both bacterial and tumor antigens. Such vaccine design provides for a straightforward, yet unique immunotherapeutic means of generating robust, non-toxic, diversified, combined antigen-specific CD4+/CD8+ T/B-cell immunity, irrespective of patient HLA repertoire also in disease associated transporter-associated with antigen processing (TAP) deficiencies. Subsequent clinical trials will further assess the full potential of this approach.

Synthetic Peptides as Vaccines

Synthetic peptide vaccines, used for the induction of T-cell and antibody responses, are an established tool for the prevention and treatment of select malignancies. Among their advantages are (1) the induction of a highly specific response, with negligible shortterm toxicity, (2) their chemical stability and absence of pathogens and other contaminating mammalian substances, and (3) their cost effective production, allowing for long-term maintenance use in therapeutic applications. However, to date, there is still no licensed peptide vaccine, suggesting that improvement in peptides’ immunogenicity is highly needed. This review will present the properties of signal peptide (SP) domains that render them an immunogenic, antigen-specific, multi-epitope protein region with key immunological advantages as vaccine candidates (VCs). Click here to download the full research article.