Protective immune response induced by cationic liposomes bearing soluble antigens improves the survival of BALB/c mice against Toxoplasma gondii RH strain

Document Type : Original Article

Authors

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

2 Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

3 Department of Parasitology and Mycology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran;Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran

4 Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran

5 Health and Treatment Network of Mehran City, Ilam University of Medical Sciences, Ilam, Iran

10.22038/ijbms.2024.82123.17770

Abstract

Objective(s): An ideal strategy to control acute or chronic toxoplasmosis can be the development and production of an effective vaccine. Liposomes as immunoadjuvants may be utilized to boost immune reactions for various antigens.
Materials and Methods:  In this study, we encapsulated soluble Toxoplasma antigen (SA) in 1, 2-Dioleoyl-3-trimethylammonium propane (DOTAP) liposomes to assess the elicited immunological response. BALB/C mice received three intramuscular injections of various formulations separated by two weeks. The kind of immune reaction that was created, the degree of protection, the percentage of BALB/c mice that survived the Toxoplasma gondii challenge, the immune reaction assessment with cytokine synthesis (IFN-γ, IL-4), and the titration of IgG isotypes were all evaluated.
Results: Compared to other groups, the liposome DOTAP + imiquimod + SA-immunized mice showed a significantly lower death rate (P<0.01). Liposome DOTAP + Imiquimod + SA had higher IgG2a and IFN-γ secretion levels than the control group (P<0.001 and P<0.0001, respectively).
Conclusion: According to the study’s findings, the liposome DOTAP + imiquimod + SA formulation generates a cellular immunological response, making it resistant to the T. gondii challenge.

Keywords

Main Subjects

References

1. Tenter AM. Toxoplasma gondii in animals used for human consumption. Memórias do Instituto Oswaldo Cruz 2009;104:364-369.
2. Ahmadpour E, Daryani A, Sharif M, Sarvi S, Aarabi M, Mizani A, et al. Toxoplasmosis in immunocompromised patients in Iran: a systematic review and meta-analysis. J Infect Dev Ctries 2014;8:1503-1510.
3. Contini C. Clinical and diagnostic management of toxoplasmosis in the immunocompromised patient. Parassitologia 2008;50:45-50.
4. Dubey JP. Toxoplasmosis of Animals and Humans: CRC press; 3rd Edition 2016.
5. Daryani A, Sarvi S, Aarabi M, Mizani A, Ahmadpour E, Shokri A, et al. Seroprevalence of Toxoplasma gondii in the Iranian general population: A systematic review and meta-analysis. Acta Trop 2014;137:185-194.
6. Zhang N-Z, Chen J, Wang M, Petersen E, Zhu X-Q. Vaccines against Toxoplasma gondii: New developments and perspectives. Expert Rev Vaccines 2013;12:1287-1299.
7. 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.
8. Moon JJ, Suh H, Bershteyn A, Stephan MT, Liu H, Huang B, et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat Mater 2011;10:243-251.
9. Dupont CD, Christian DA, Hunter CA. Immune response and immunopathology during toxoplasmosis. Semin Immunopathol 2012;34:793-813.
10. 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.
11. Mehravaran A, Jaafari MR, Jalali SA, Khamesipour A, Tafaghodi M, Hojatizade M, et al. Cationic immune stimulating complexes containing soluble Leishmania antigens: Preparation, characterization and in vivo immune response evaluation. Iran J Immunol 2015;12:274-287.
12. Schwendener RA. Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines 2014;2:159-182.
13. Mehravaran A, Jaafari MR, Jalali SA, Khamesipour A, Ranjbar R, Hojatizade M, et al. The role of ISCOMATRIX bilayer composition to induce a cell mediated immunity and protection against leishmaniasis in BALB/c mice. Iran J Basic Med Sci 2016;19:178-186.
14. Jafari I, Shargh VH, Shahryari M, Abbasi A, Jaafari MR, Khamesipour A, et al. Cationic liposomes formulated with a novel whole Leishmania lysate (WLL) as a vaccine for leishmaniasis in murine model. Immunobiology 2018;223:493-500.
15.  Wickelgren I. Immunology. Targeting the tolls. Science 2006; 312:184-187. 
16. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004;5:987-995.
17. Johnston D, Bystryn J-C. Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine. Vaccine 2006;24:1958-1965.
18. Daryani A, Sharif M, Kalani H, Rafiei A, Kalani F, Ahmadpour E. Electrophoretic patterns of Toxoplasma gondii excreted/secreted antigens and their role in induction of the humoral immune response. Jundishapur J Microbiol 2014;7:e9525.
19. Bainor A, Chang L, McQuade TJ, Webb B, Gestwicki JE. Bicinchoninic acid (BCA) assay in low volume. Anal Biochem 2011;410:310-312.
20. O’Hagan DT, Singh M. Microparticles as vaccine adjuvants and delivery systems. Expert Rev Vaccines 2003;2:269-283.
21. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 2005;4:145-160.
22. Azadi Y, Ahmadpour E, Hamishehkar H, Daryani A, Spotin A, Mahami-Oskouei M, et al. Quantification of Toxoplasma gondii in the tissues of BALB/c mice after immunization with nanoliposomal excretory-secretory antigens using Real-Time PCR. Comp Immunol Microbiol Infect Dis 2018;59:52-56.
23. Rahimi MT, Sarvi S, Sharif M, Abediankenari S, Ahmadpour E, Valadan R, et al. Immunological evaluation of a DNA cocktail vaccine with co-delivery of calcium phosphate nanoparticles (CaPNs) against the Toxoplasma gondii RH strain in BALB/c mice. Parasitol Res 2017;116:609-616.
24. Rezaei F, Sarvi S, Sharif M, Hejazi SH, Pagheh AS, Aghayan SA, et al. A systematic review of Toxoplasma gondii antigens to find the best vaccine candidates for immunization. Microb Pathog 2019; 126: 172–184.
25. Wang JL, Zhang NZ, Li TT, He JJ, Elsheikha HM, Zhu XQ. Advances in the development of anti-Toxoplasma gondii Vaccines: Challenges, Opportunities, and Perspectives. Trends Parasitol 2019 ;35:239-253. 
26. Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, Yarovinsky F, Herbert DR, Bzik DJ, Denkers EY. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog 2011;7: e1002236.
27. Maji M, Mazumder S, Bhattacharya S, Choudhury ST, Sabur A, Shadab M, et al. A lipid based antigen delivery system efficiently facilitates MHC class-I antigen presentation in dendritic cells to stimulate CD8+ T cells. Sci Rep 2016;6:27206.
28. Dupont CD, Christian DA, Hunter CA.  Immune response and immunopathology during toxoplasmosis. Semin Immunopathol 2012;34:793-813.
29. Wang N, Chen M, Wang T. Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization. J Control Release 2019;303:130-150.
30. Nishikawa Y, Inoue N, Makala L, Nagasawa H. A role for balance of interferon-gamma and interleukin-4 production in protective immunity against Neospora caninum infection. Vet Parasitol 2003;116:175-184.
31. Sun B, Xia T. Nanomaterial-based vaccine adjuvants. J Mater Chem B 2016;4:5496-5509.
32. Bal SM, Hortensius S, Ding Z, Jiskoot W, Bouwstra JA. Co-encapsulation of antigen and Toll-like receptor ligand in cationic liposomes affects the quality of the immune response in mice after intradermal vaccination. Vaccine 2011;29:1045-1052.
33. 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;132:403-409.
34. Asgari Q, Keshavarz H, Shojaee S, Motazedian MH, Mohebali M, Miri R, et al. In vitro and in vivo potential of RH strain of Toxoplasma gondii (Type I) in tissue cyst forming. Iran J Parasitol 2013;8:367-375.
35. Azadi Y, Ahmadpour E, Ahmadi A. Targeting strategies in therapeutic applications of toxoplasmosis: Recent advances in liposomal vaccine delivery systems. Curr Drug Targets 2020;21:541-558. 
36. Chyb M, Dziadek B, Dzitko K, Ferra BT, Kawka M, Holec-Gąsior L, Gatkowska J. Evaluation of long-term immunity and protection against T. gondii after immunization with multivalent recombinant chimeric T. gondii proteins. Sci Rep 2023;10:12976-12988.
37. Dodangeh S, Daryani A, Sharif M, Aghayan SA, Pagheh AS, Sarvi S, Rezaei F. A systematic review on efficiency of microneme proteins to induce protective immunity against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis 2019;38:617-629. 
38. Kavand M, Mehravaran A, Pahlavani E, Mirahmadi H, Akhtari J, Rahmati-Balaghaleh M, et al. Evaluation of survival rate using liposome containing soluble antigens (SA) against Toxoplasma gondii infection in BALB/c mice. Nanomed J 2021;8:179-186.
39. Abdollahi SH, Ebrahimi Shahmabadi H, Kazemi Arababadi M, Askari, Khanamani Falahatipour S. The immune response against Toxoplasma gondii in BALB/c mice induced by mannosemodifed nanoliposome of excreted/secreted antigens. Parasitol Res 2021;120:2855-2861.
40. 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.
41. Dockrell D, Kinghorn G. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother 2001;48:751-755.
42. Peine KJ, Gupta G, Brackman DJ, Papenfuss TL, Ainslie KM, Satoskar AR, et al. Liposomal resiquimod for the treatment of Leishmania donovani infection. J Antimicrob Chemother 2013;69:168-175.
43. Brito LA, Malyala P, O’Hagan DT. Vaccine adjuvant formulations: A pharmaceutical perspective. Semin Immunol 2013; 25:130-145.
44. Zhang WW, 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.
45. Othoro C, Johnston D, Lee R, Soverow J, Bystryn JC, Nardin E. Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun 2009;77:739-748.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 3
March 2025
Pages 347-354

Files

Share

How to cite

Statistics