Characterization of Leishmania major antigen-liposomes that protect BALB/c mice against cutaneous leishmaniasis.
Leishmania major antigen-liposomes prepared as dehydration-rehydration vesicles (DRV) and composed of equimolar amounts of L-alpha-distearoyl phosphatidylcholine and cholesterol confer high-level host-protective immunity against virulent homologous challenge to susceptible BALB/c mice. Physical and antigenic characterization of these protective liposomes is described. Both empty and L. major antigen-DRV were multilamellate and heterogeneous in size, ranging from 0.10 to 2.00 microns. Although the liposomes were made by using a crude mixture of promastigote antigens, lipophosphoglycan covered the liposome surface; this was demonstrated by immunogold electron microscopy. Application of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis revealed preferential entrapment of the 63-kilodalton promastigote protease (gp63) into the DRV. We suggest that our L. major antigen-DRV merit further study because of their preferential entrapment of these two host protective antigens together with their long in vivo half-life. In addition, this report illustrates that intravenous or subcutaneous immunization of BALB/c mice with the same limited subset of protective antigens, predominantly lipophosphoglycan and gp63, within DRV liposomes leads to either protection and low splenic interleukin-3 production or to nonprotection and high splenic interleukin-3 production, respectively. This was consistent with our hypothesis that differential antigen presentation after administration of the same immunogen by the intravenous or the subcutaneous route results in differential T-cell activation.
Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
L P
LP
Kahl
R
R
Lelchuk
C A
CA
Scott
J
J
Beesley
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology; D015153:Blotting, Western; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007114:Immunization; D007377:Interleukin-3 / Q000096:biosynthesis; D007895:Leishmania tropica / Q000276:immunology*; D007896:Leishmaniasis / Q000517:prevention & control*; D008081:Liposomes / Q000276:immunology*; D008214:Lymphocytes / Q000378:metabolism; D008666:Metalloendopeptidases; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology / Q000648:ultrastructure; D013154:Spleen / Q000166:cytology
D000953:Antigens, Protozoan; D004337:Drug Carriers; D007377:Interleukin-3; D008081:Liposomes; D015800:Protozoan Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania