Evaluation of Immune Response against Leishmaniasis in BALB/c Mice Immunized with Cationic DOTAP/DOPE/CHOL Liposomes Containing Soluble Leishmania major Antigens
Abstract
Background: Whole killed Leishmania vaccine reached phase III clinical trials but failed to display significant efficacy in human mainly due to limited Th1 inducer adjuvant. Liposomes consisting of 1, 2-dioleoyl-3trimethylammonium-propane (DOTAP) bearing an inherent adjuvanticity and 1, 2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) is well known to intensify the efficacy of positively charged liposomes.
Methods: Soluble Leishmania major antigens (SLA) encapsulated in cationic liposomes using lipid film method in 2016). BALB/c mice were immunized subcutaneously (SC), three times in a 2-wk interval, with Lip (DOTAP)-SLA+, Lip (DOTAP/DOPE)-SLA+, Lip (DOTAP/DOPE/CHO)-SLA+, Lip (DOTAP/DOPE/CHO), Lip (DOPE/CHO), SLA or HEPES buffer. At week 2 after the last booster injection, immunized mice have challenged SC in the footpad with L. major parasites. To investigate the rate of protection and the type of immune response generated in mice, lesions development was assessed, IL-4 and IFN-γ levels with the ratio of IgG2a/IgG1 isotype were studied to describe the type of generated immune response.
Results: Mice immunized with all liposomal form of SLA showed smaller footpad swelling and lower parasite burden in the spleen and footpad compared to the group of mice received buffer. However, these formulations did not show protection against leishmaniosis because of a generated mixed Th1/Th2 response in mice characterized by high production of IFN-γ and IL4 and a high titer of IgG1 and IgG2a antibody.
Conclusion: Immunization with Lip (DOTAP/DOPE/CHO)-SLA+ was not an appropriate strategy to protect mice against leishmaniosis.
Dumonteil E, Maria Jesus R-S, Javier E-O, Maria del Rosario Ga-M. DNA vaccines induce partial protection against Leishmania mexicana. Vaccine. 2003;21(17):2161-8.
Mutiso JM, Macharia JC, Kiio MN, Ichagichu JM, Rikoi H, Gicheru MM. Development of Leishmania vaccines: predicting the future from past and present experience. J. Biomed Res. 2013;27(2):85.
Kamhawi S, Oliveira F, Valenzuela JG. Using humans to make a human leishmaniasis vaccine. Sci Transl Med. 2014;6(234):234fs18.
Kumar R, Engwerda C. Vaccines to prevent leishmaniasis. Clin & Translational Immunol. 2014;3(3):e13.
Pearson RD, de Queiroz Sousa A. Clinical spectrum of leishmaniasis. Clin Infect Dis. 1996:1-11.
Sacks D, Kamhawi S. Molecular Aspects of Parasite-Vector and Vector-Host Interactions in Leishmaniasis 1. Ann Rev Microbiol. 2001;55(1):453-83.
Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev. 2006;19(1):111-26.
Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop Med & Int Health. 2001;6(11):849-54.
Khamesipour A, Dowlati Y, Asilian A, Hashemi-Fesharki R, Javadi A, Noazin S, et al. Leishmanization: use of an old method for evaluation of candidate vaccines against leishmaniasis. Vaccine. 2005;23(28):3642-8.
Alvar J, Croft SL, Kaye P, Khamesipour A, Sundar S, Reed SG. Case study for a vaccine against leishmaniasis. Vaccine. 2013;31:B244-B9.
Noazin S, Modabber F, Khamesipour A, Smith PG, Moulton LH, Nasseri K, et al. First generation leishmaniasis vaccines: a review of field efficacy trials. Vaccine. 2008;26(52):6759-67.
Stanley AC, Engwerda CR. Balancing immunity and pathology in visceral leishmaniasis. Immunol Cell Biol. 2006;85(2):138-47.
Badiee A, Shargh VH, Khamesipour A, Jaafari MR. Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends. Vaccine. 2013;31(5):735-49.
Khamesipour A, Rafati S, Davoudi N, Maboudi F, Modabber F. Leishmaniasis vaccine candidates for development: a global overview. Indian J Med Res. 2006;123(3):423-38.
Badiee A, Jaafari MR, Samiei A, Soroush D, Khamesipour A. Coencapsulation of CpG oligodeoxynucleotides with recombinant Leishmania major stress-inducible protein 1 in liposome enhances immune response and protection against leishmaniasis in immunized BALB/c mice. Clin Vaccine Immunol. 2008;15(4):668-74.
Henriksen-Lacey M, Bramwell VW, Christensen D, Agger E-M, Andersen P, Perrie Y. Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. J Control Release. 2010;142(2):180-6.
Brgles M, Habjanec L, Halassy B, Tomašić J. Liposome fusogenicity and entrapment efficiency of antigen determine the Th1/Th2 bias of antigen-specific immune response. Vaccine. 2009;27(40):5435-42.
Copland MJ, Rades T, Davies NM, Baird MA. Lipid based particulate formulations for the delivery of antigen. Immunol Cell Biol. 2005;83(2):97-105.
Bajaj A, Mishra SK, Kondaiah P, Bhattacharya S. Effect of the headgroup variation on the gene transfer properties of cholesterol based cationic lipids possessing ether linkage. Biochim Biophys Acta (BBA)-Biomembranes. 2008;1778(5):1222-36.
Lonez C, Vandenbranden M, Ruysschaert J-M. Cationic liposomal lipids: from gene carriers to cell signaling. Prog Lipid Res. 2008;47(5):340-7.
Yan W, Chen W, Huang L. Mechanism of adjuvant activity of cationic liposome: phosphorylation of a MAP kinase, ERK and induction of chemokines. Mol Immunol. 2007;44(15):3672-81.
Tanaka T, Legat A, Adam E, Steuve J, Gatot JS, Vandenbranden M, et al. DiC14‐amidine cationic liposomes stimulate myeloid dendritic cells through Toll‐like receptor 4. Eur j immunol. 2008;38(5):1351-7.
Javadian E, Nadim A, Tahvildare-Bidruni G, Assefi V. Epidemiology of cutaneous leishmaniasis in Iran: B. Khorassan Part V: Report on a focus of zoonotic cutaneous leishmaniasis in Esferayen. Bull Soc Pathol Exot Filiales. 1975;69(2):140-3.
Sharifi I, Fekri AR, Aflatonian M-R, Khamesipour A, Nadim A, Mousavi M-RA, et al. Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. The Lancet. 1998;351(9115):1540-3.
Momeni AZ, Jalayer T, Emamjomeh M, Khamesipour A, Zicker F, Ghassemi RL, et al. A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran. Vaccine. 1999;17(5):466-72.
Scott P, Pearce E, Natovitz P, Sher A. Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes. J.Immunol. 1987;139(1):221-7.
Kirby C, Gregoriadis G. Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Nat Biotechnol. 1984;2(11):979-84.
Iman M, Huang Z, Szoka Jr FC, Jaafari MR. Characterization of the colloidal properties, in vitro antifungal activity, antileishmanial activity and toxicity in mice of a distigmasterylhemisuccinoyl-glycero-phosphocholine liposome-intercalated amphotericin B. Int J.pharmac. 2011;408(1):163-72.
Jaafari MR, Ghafarian A, Farrokh-Gisour A, Samiei A, Kheiri MT, Mahboudi F, et al. Immune response and protection assay of recombinant major surface glycoprotein of Leishmania (rgp63) reconstituted with liposomes in BALB/c mice. Vaccine. 2006;24(29):5708-17.
Badiee A, Jaafari MR, Khamesipour A. Leishmania major: Immune response in BALB/c mice immunized with stress-inducible protein 1 encapsulated in liposomes. Exp Parasitol. 2007;115(2):127-34.
Huang Z, Jaafari MR, Szoka FC. Disterolphospholipids: nonexchangeable lipids and their application to liposomal drug delivery. Angew Chem. 2009;121(23):4210-3.
Korsholm KS, Andersen PL, Christensen D. Cationic liposomal vaccine adjuvants in animal challenge models: overview and current clinical status. Exp Rev vaccines. 2012;11(5):561-77.
Lonez C, Vandenbranden M, Ruysschaert J-M. Cationic lipids activate intracellular signaling pathways. Adv Drug Deliver Rev. 2012;64(15):1749-58.
Schwendener RA. Liposomes as vaccine delivery systems: a review of the recent advances. Therapeutic advances in vaccines. 2014;2(6):159-82.
Vangasseri DP, Cui Z, Chen W, Hokey DA, Falo Jr LD, Huang L. Immunostimulation of dendritic cells by cationic liposomes. Mol Membr Biol. 2006;23(5):385-95.
Hafez I, Maurer N, Cullis P. On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther. 2001;8(15):1188-96.
Yan W, Chen W, Huang L. Reactive oxygen species play a central role in the activity of cationic liposome based cancer vaccine. J Control Release. 2008;130(1):22-8.
Firouzmand H, Badiee A, Khamesipour A, Heravi Shargh V, Alavizadeh SH, Abbasi A, et al. Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA). Acta tropica. 2013;128(3):528-35.
Sułkowski W, Pentak D, Nowak K, Sułkowska A. The influence of temperature, cholesterol content and pH on liposome stability. J Mol Struct. 2005;744:737-47.
Ignatius R, Mahnke K, Rivera M, Hong K, Isdell F, Steinman RM, et al. Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8+ T-cell responses in vivo. Blood. 2000;96(10):3505-13.
Skeiky YA, Coler RN, Brannon M, Stromberg E, Greeson K, Thomas Crane R, et al. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine. 2002;20(27):3292-303.
Bhowmick S, Ravindran R, Ali N. Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response. Vaccine. 2007;25(35):6544-56.
Afrin F, Rajesh R, Anam K, Gopinath M, Pal S, Ali N. Characterization of Leishmania donovani antigens encapsulated in liposomes that induce protective immunity in BALB/c mice. Infect Immun. 2002;70(12):6697-706.
Shargh VH, Jaafari MR, Khamesipour A, Jaafari I, Jalali SA, Abbasi A, et al. Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis. Vaccine. 2012;30(26):3957-64.
O'Hagan DT, Christy NM, Davis SS. Particulates and lymphatic drug delivery: Boca Raton, FL: CRC Press Inc; 1992.
Watson DS, Endsley AN, Huang L. Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. Vaccine. 2012;30(13):2256-72.
Brewer JM, Tetley L, Richmond J, Liew FY, Alexander J. Lipid vesicle size determines the Th1 or Th2 response to entrapped antigen. The J. Immunol. 1998;161(8):4000-7.
Badiee A, Khamesipour A, Samiei A, Soroush D, Shargh VH, Kheiri MT, et al. The role of liposome size on the type of immune response induced in BALB/c mice against leishmaniasis: rgp63 as a model antigen. Exp Parasitol. 2012;132(4):403-9.
Smith Korsholm K, Agger EM, Foged C, Christensen D, Dietrich J, Andersen CS, et al. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology. 2007;121(2):216-26.
Cui Z, Han S-J, Vangasseri DP, Huang L. Immunostimulation mechanism of LPD nanoparticle as a vaccine carrier. Molecular pharmaceutics. 2005;2(1):22-8.
| Files | ||
| Issue | Vol 14 No 1 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v14i1.719 | |
| Keywords | ||
| L. major; BALB/c mice Leishmania vaccine Cationic liposomes Dioleoyl-3trimethylammonium-propane | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
