Comparison of numerous delivery systems for the induction of cytotoxic T lymphocytes by immunization

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Abstract
A variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid DNA were tested for their ability to induce CD8+ cytotoxic T lymphocytes (CTL) against a well‐defined epitope (amino acids 252–260) from the circumsporozoite (CS) protein of Plasmodium berghei. We compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. The majority of these vaccines did not induce high CTL responses in the spleens of immunized mice. However, both a yeast‐derived Ty virus‐like particle expressing the optimal nine‐amino acid epitope SYIPSAEKI from the CS protein (CSP‐VLP) and a lipid‐tailed peptide of this same sequence induced high levels of the major histocompatibility complex (MHC) class I‐restricted CTL with one and three subcutaneous immunizations, respectively. Moreover, these CTL were able to recognize naturally processed antigen expressed by a recombinant vaccinia virus. The levels of CTL induced by CSP‐VLP could be augmented by co‐immunization with certain cytokines. Target cells pulsed with CSP‐VLP were recognized and lysed, showing that the particles were effectively processed and presented through MHC class I presentation pathway. The levels of CTL induced using CSP‐VLP and lipopeptides are comparable to those observed after immunization with multiple doses of irradiated sporozoites.