Liposomes containing the imiquimod adjuvant as a vaccine in the cutaneous leishmaniasis model

Document Type : Research Paper

Authors

1 Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis institute, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Parasitology and Mycology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

3 Toxoplasmosis Research Center, Department of Medical Nanotechnology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Objective(s): Attempts to produce vaccines for leishmaniasis need adjuvants to trigger the kind of immune reaction required for protection. In this study, we examined the properties of the TLR7 agonist imiquimod, a vaccine adjuvant, making use of a live model of infection where the immune reactions could be identified prior to and following the challenge of infection.
Materials and Methods: The liposomes of EPC containing the imiquimod adjuvant were prepared and characterized for protein concentration, surface charge, and particle size. Vaccination was done using the soluble Leishmania antigen (SLA) as a first-generation vaccine model in the liposomal state to vaccinate BALB/c mice against the challenge of leishmania major. BALB/c mice were vaccinated subcutaneously, three times at a two-week interval. Parasite burden, footpad swelling, IgG isotype, as well as the level of IL-4 and IFN-γ were assessed as the protection criteria.
Results: The group of mice vaccinated by Lip+Imiquimod+SLA demonstrated a lower amount of footpad swelling and parasite burden than the buffer group. In addition, the highest level of IFN-γ and the lowest level of IL-4 production was noticed in the splenocytes of the mice vaccinated with the formulation of Lip+Imiquimod+SLA.
Conclusion: These results imply that imiquimod added to the formulation of liposomes is able to modulate the immune reaction of the BALB/c mice vaccinated preferably to a Th1 reaction rather than a Th2 reaction which can also lead to partial protection against the challenge of Leishmania.

Keywords

References

1.WHO/Leishmaniasis,WHO,http://www.who.int/leishmaniasis/en/. 2017; Accessed date: 8 November 2017.
2.Modabber F. Leishmaniasis vaccines: past, present and future. Int J Antimicrob Agents. 2010; 36: S58-S61.
3.Evans KJ, Kedzierski L. Development of vaccines against visceral leishmaniasis. J Trop Med. 2012; 2012: 892817
4.Askarizadeh A, Jaafari MR, Khamesipour A, Badiee A. Liposomal adjuvant development for leishmaniasis vaccines. Ther Adv Vaccines. 2017; 5: 85-101.
5.Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002; 2: 845-58.
6.Scott P, Novais FO. Cutaneous leishmaniasis: immune responses in protection and pathogenesis. Nat Rev Immunol. 2016; 16: 581-592.
7.Martins VT, Chávez-Fumagalli MA, Costa LE, Martins AM, Lage PS, Lage DP, Duarte MC, Valadares DG, Magalhães RD, Ribeiro TG. Antigenicity and protective efficacy of a Leishmania amastigote-specific protein, member of the super-oxygenase family, against visceral leishmaniasis. PLoS Negl Trop Dis. 2013; 7: e2148.
8.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: 2256-2272.
9.Apostolopoulos V. Vaccine delivery methods into the future. Multidisciplinary Digital Publishing Institute; 2016.
10.Nordly P, Agger EM, Andersen P, Nielsen HM, Foged C. Incorporation of the TLR4 agonist monophosphoryl lipid A into the bilayer of DDA/TDB liposomes: physico-chemical characterization and induction of CD8+ T-cell responses in vivo. Pharm Res. 2011; 28: 553-562.
11.Moon JJ, Suh H, Bershteyn A, Stephan MT, Liu H, Huang B, Sohail M, Luo S, Um SH, Khant H. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat Mater. 2011; 10: 243-251.
12.Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev. 2012; 64: 37-48.
13.Mazumder S, Maji M, Ali N. Potentiating effects of MPL on DSPC bearing cationic liposomes promote recombinant GP63 vaccine efficacy: high immunogenicity and protection. PLoS Negl Trop Dis. 2011; 5: e1429.
14.Joshi MD, Unger WJ, Storm G, van Kooyk Y, Mastrobattista E. Targeting tumor antigens to dendritic cells using particulate carriers. J Control Release. 2012; 161: 25-37.
15.Smith DM, Simon JK, Baker Jr JR. Applications of nanotechnology for immunology. Nat Rev Immunol. 2013; 13: 592-605.
16.Krishnan L, Sad S, Patel GB, Sprott GD. Archaeosomes induce enhanced cytotoxic T lymphocyte responses to entrapped soluble protein in the absence of interleukin 12 and protect against tumor challenge. Cancer Res. 2003; 63: 2526-2534.
17.Mehravaran A, Jaafari MR, Jalali SA, Khamesipour A, Tafaghodi M, Hojatizade M, Badiee A. The role of surface charge of ISCOMATRIX nanoparticles on the type of immune response generated against Leishmaniasis in BALB/c mice. Nanomed J. 2015; 2: 249-260.
18.Mehravaran A, Jaafari MR, Jalali SA, Khamesipour A, Tafaghodi M, Hojatizade M, Abbasi A, Badiee A. Cationic immune stimulating complexes containing soluble Leishmania antigens: preparation, characterization and in vivo immune response evaluation. IJI. 2015; 12: 274-287.
19.Mehravaran A, Jaafari MR, Jalali SA, Khamesipour A, Ranjbar R, Hojatizade M, Badiee A. The role of ISCOMATRIX bilayer composition to induce a cell mediated immunity and protection against leishmaniasis in BALB/c mice. IJBMS. 2016; 19: 178-86.
20.Bhowmick S, Ali N. Recent developments in leishmaniasis vaccine delivery systems. Expert Opin Drug Deliv. 2008; 5: 789-803.
21.Raman VS, Reed SG, Duthie MS, Fox CB, Matlashewski G. Adjuvants for Leishmania vaccines: from models to clinical application. Front Immunol. 2012; 3: 144.
22.Miranda-Verástegui C, Llanos-Cuentas A, Arevalo I, Ward B, Matlashewski G. Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru. Clin Infect Dis. 2005; 40: 1395-1403.
23.Arevalo I, Ward B, Miller R, Meng T-C, Najar E, Alvarez E, Matlashewski G, Alejandro L-C. Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 2001; 33: 1847-1851.
24.Dockrell D, Kinghorn G. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother. 2001; 48: 751-755.
25.Khamesipour A, Rafati S, Davoudi N, Maboudi F, Modabber F. Leishmaniasis vaccine candidates for development: a global overview. Indian J Med Res. 2006; 123: 423-38.
26.ALIMOHAMMADIAN MH, HAKIMI H, NIKSERESHT M. The P Reparation And Evaluation Of Reference Leishmanin From Leishmania Major For Use In Man For Diagnos Tic And Experimental Purposes. MJIRI. 1993; 7: 23-28.
27.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: 221-227.
28.Bainor A, Chang L, McQuade TJ, Webb B, Gestwicki JE. Bicinchoninic acid (BCA) assay in low volume. Anal Biochem. 2011; 410: 310-312.
29.Torchilin PV, Torchilin V, Torchilin V, Weissig V. Liposomes: a practical approach: Oxford University Press; 2003.
30.Firouzmand H, Badiee A, Khamesipour A, Heravi Shargh V, Alavizadeh SH, Abbasi A, Jaafari MR. Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA). Acta Trop. 2013; 128: 528-535.
31.de Barros NB, Aragao Macedo SR, Ferreira AS, Tagliari MP, Kayano AM, Nicolete LDF, Soares AM, Nicolete R. ASP49-phospholipase A2-loaded liposomes as experimental therapy in cutaneous leishmaniasis model. Int Immunopharmacol. 2018; 55: 128-132.
32.Shargh VH, Jaafari MR, Khamesipour A, Jaafari I, Jalali SA, Abbasi A, Badiee A. 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: 3957-3964.
33.Hojatizade M, Soleymani M, Tafaghodi M, Badiee A, Chavoshian O, Jaafari MR. Chitosan Nanoparticles Loaded with Whole and Soluble Leishmania Antigens, and Evaluation of Their Immunogenecity in a Mouse Model of Leishmaniasis. IJI. 2018; 15: 281-293.
34.Jafari I, Heravi Shargh V, Shahryari M, Abbasi A, Jaafari MR, Khamesipour A, Badiee A. Cationic liposomes formulated with a novel whole Leishmania lysate (WLL) as a vaccine for leishmaniasis in murine model. Immunobiology. 2018; 223: 493-500.
35.Das A, Ali N. Correction: Combining Cationic Liposomal Delivery with MPL-TDM for Cysteine Protease Cocktail Vaccination against Leishmania donovani: Evidence for Antigen Synergy and Protection. PLoS Negl Trop Dis. 2015; 9: e0004185.
36.Badiee A, Heravi Shargh V, Khamesipour A, Jaafari MR. Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends. Vaccine. 2013; 31: 735-749.
37.Iborra S, Solana JC, Requena JM, Soto M. Vaccine candidates against leishmania under current research. Expert Rev Vaccines. 2018; 17:323-334.
38.Zhang W-W, Matlashewski G. Immunization with a Toll-like receptor 7 and/or 8 agonist vaccine adjuvant increases protective immunity against Leishmania major in BALB/c mice. Infect Immun. 2008; 76: 3777-3783.
39.Khamesipour A. Therapeutic vaccines for leishmaniasis. Expert Opin Biol Ther. 2014; 14:1641-9.
40.Buates S, Matlashewski G. Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: efficacy and mode of action. J Infect Dis. 1999; 179: 1485-1494.
41.Buates S, Matlashewski G. Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis. Antimicrob Agents Chemother. 2001; 45:1137-1142.
42.Naseri H, Eskandari F, Jaafari M, Khamesipour A, Abbasi A, Badiee A. PEG ylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model. Parasite Immunol. 2017; 39: e12492.
43.Badiee A, Jaafari MR, Khamesipour A, Samiei A, Soroush D, Kheiri MT, Barkhordari F, McMaster WR, Mahboudi F. Enhancement of immune response and protection in BALB/c mice immunized with liposomal recombinant major surface glycoprotein of Leishmania (rgp63): the role of bilayer composition. Colloids Surf B Biointerfaces. 2009; 74: 37-44.
44.Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S. Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway. Nat Immunol. 2002; 3: 196-200.
45.Mehravaran A, Nasab MR, Mirahmadi H, Sharifi I, Alijani E, Nikpoor AR, Akhtari J. Protection induced by Leishmania Major antigens and the imiquimod adjuvant encapsulated on liposomes in experimental cutaneous leishmaniasis. Infect Genet Evol. 2019; 70: 27-35.
46.Mehravaran A, Rezaei Nasab M, Mirahmadi H, Sharifi I, Alijani E, Nikpoor AR, Akhtari J, Hojatizade M. Immunogenicity and protection effects of cationic liposome containing imiquimod adjuvant on leishmaniasis in BALB/c mice. IJBMS. 2019; 22: 1-10.
47.Emami T, Rezayat SM, Khamesipour A, Madani R, Habibi G, Hojatizade M, Jaafari MR. The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome. Artif Cells Nanomed Biotechnol. 2018; 46: 324-333.
Nanomedicine Journal
Volume 7, Issue 1
January 2020
Pages 29-39

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