The role of liposome charge on immune response generated in BALB/c mice immunized with recombinant major surface glycoprotein of Leishmania (rgp63).
Liposomes as a lipid-based system have been shown to be an effective adjuvant formulation. In this study, the role of liposome charge in induction of a Th1 type of immune response and protection against leishmaniasis in BALB/c mice was studied. Liposomes containing rgp63 were prepared by Dehydration-Rehydration Vesicle (DRV) method. Neutral liposomes consisted of dipalmitoylphosphatidylcholine and cholesterol. Positively and negatively charged liposomes were prepared by adding dimethyldioctadecylammonium bromide (DDAB) or dicetyl phosphate (DCP) to the neutral liposome formulation, respectively. Female BALB/c mice were immunized subcutaneously with negatively, positively charged or neutral liposomes encapsulated with rgp63, rgp63 in soluble form or PBS, three times in 3week intervals. The extent of protection and type of immune response generated were studied in different groups of mice. The group of mice immunized with rgp63 encapsulated in neutral liposomes showed a significantly (P<0.01) smaller footpad swelling upon challenge with Leishmania major compared with positively or negatively charged liposomes. The mice immunized with neutral liposomes also showed a significantly (P<0.01) the lowest splenic parasite burden, the highest IgG2a/IgG1 ratio and IFN-gamma production and the lowest IL-4 level compared to the other groups. The results indicated that a Th1 type of immune response was induced in mice immunized with neutral liposomes more efficiently than positively charged liposomes and conversely negatively charged liposomes induced a Th2 type of immune response.
Badiee
Ali
A
School of Pharmacy, Biotechnology Research Center and Pharmaceutical Research Center, Mashhad University of Medical Sciences, Vakil-Abad Blvd, P.O. Box 91775-1365, Mashhad, Khorasan, Iran.
Jaafari
Mahmoud R
MR
Khamesipour
Ali
A
Samiei
Afshin
A
Soroush
Dina
D
Kheiri
Masoumeh Tavassoti
MT
Barkhordari
Farzaneh
F
McMaster
W Robert
WR
Mahboudi
Fereidoun
F
D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D008081:Liposomes / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma