Comparison of numerous delivery systems for the induction of cytotoxic T lymphocytes by immunization.
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.
Allsopp
C E
CE
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, GB.
Plebanski
M
M
Gilbert
S
S
Sinden
R E
RE
Harris
S
S
Frankel
G
G
Dougan
G
G
Hioe
C
C
Nixon
D
D
Paoletti
E
E
Layton
G
G
Hill
A V
AV
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology; D016503:Drug Delivery Systems; D000939:Epitopes / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000276:immunology; D014771:Virion / Q000276:immunology
D000953:Antigens, Protozoan; D000939:Epitopes; D014614:Vaccines, Synthetic