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

Catherine E M Allsopp, Magdalena Plebanski, Sarah Gilbert, Robert E. Sinden, Steve Harris, Gadi Frankel, Gordon Dougan, Catarina Hioe, Douglas Nixon, Enzo Paoletti, Guy Lajton, Adrian V S Hill

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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 Plasmonium 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 coimmunization 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.

Original languageEnglish
Pages (from-to)1951-1959
Number of pages9
JournalEuropean Journal of Immunology
Issue number8
Publication statusPublished - 1996
Externally publishedYes


  • Cytotoxic T lymphocyte
  • Malaria
  • Plasmodium berghei
  • Vaccine

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