Effective immunization of mice against cutaneous leishmaniasis using an intrinsically adjuvanted synthetic lipopeptide vaccine.
Two peptides representing predicted T-cell epitopes of gp63, a major surface glycoprotein of the parasite Leishmania major, were used in vaccines tested in a murine model of cutaneous leishmaniasis. Either subcutaneous or intraperitoneal immunization in saline with a peptide representing gp63 amino acids 467-482 (p467) significantly protected CBA mice against the development of severe cutaneous lesions only when the peptide was intrinsically adjuvanted by covalently adding a lauryl-cysteine moiety (LC-p467) to its amino terminus during synthesis. In marked contrast, administration of p467 alone, cysteinyl-p467 or gp63 protein in saline resulted in some disease exacerbation. Splenic cells of LC-p467 immunized mice stimulated in vitro with LC-p467 displayed strong proliferative responses and secretion of IL-2, IFN-tau and GM-CSF (but not IL-4 and IL-10) suggesting that immunization with the lipopeptide induced the TH1 type cytokine responses associated with cell-mediated immunity. The safety, efficacy, ease of production and standardization of such lipopeptide vaccines suggest that they have significant potential for the development of vaccines for humans against leishmaniasis or other parasitic or viral diseases that require cell-mediated immunity for protection.
Frankenburg
S
S
Department of Dermatology, Hadassah Medical Organization, Jerusalem, Israel.
Axelrod
O
O
Kutner
S
S
Greenblatt
C L
CL
Klaus
S N
SN
Pirak
E A
EA
McMaster
R
R
Lowell
G H
GH
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008074:Lipoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D008074:Lipoproteins; D010455:Peptides; D014614:Vaccines, Synthetic