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Detection of Toxoplasma gondii Infections using Virus-Like Particles Displaying T. gondii ROP4 Antigen

  • Kim, Min-Ju (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Mao, Jie (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Kang, Hae-Ji (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Chu, Ki-Back (Department of Medical Zoology, School of Medicine, Kyung Hee University) ;
  • Quan, Fu-Shi (Department of Medical Zoology, School of Medicine, Kyung Hee University)
  • Received : 2021.10.07
  • Accepted : 2021.12.08
  • Published : 2021.12.31

Abstract

Toxoplasma gondii ME49 infections are typically diagnosed by serological tests. However, serological diagnosis of RH strain-induced toxoplasmosis remains unknown. In order to develop seradiagnosis of above 2 kinds of infections, we generated recombinant virus-like particles (VLPs) displaying the T. gondii rhoptry protein 4 (ROP4) and evaluated their potential in T. gondii ME49 or RH strain infection diagnostics. Mice were orally infected with either the tachyzoites of T. gondii (RH) or cysts of T. gondii (ME49) at various dosages, and sera were collected at regular intervals. ELISA-based serological tests were performed to assess IgG, IgM, and IgA antibody responses against ROP4 VLP antigen and tissue lysate antigen (TLA). Compared to TLA, IgG, IgM, and IgA levels to ROP4 VLP antigen were significantly higher in the sera of T. gondii RH-infected mice 1 and 2 week post-infection (PI). T. gondii-specific IgG antibody was detected at 1, 2, 4, and 8 week PI in the T. gondii ME49-infected mice with infection dose-dependent manner. These results indicated that the ROP4 VLP antigen was highly sensitive antigens detecting T. gondii RH and ME49 antibodies at an early stage.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) (2018R1A6A1A03025124), the Ministry of Health & Welfare, Republic of Korea (HV20C0085, HV20C0142).

References

  1. Halonen SK, Weiss LM. Neuroparasitology and Tropical Neurology: Chapter 8. Toxoplasmosis. Handbook of Clinical Neurology. Amsterdam, The Netherlands. Elsevier. 2013, pp 125-145.
  2. Yarovinsky F. Toll-like receptors and their role in host resistance to Toxoplasma gondii. Immunol Lett 2008; 119: 17-21. https://doi.org/10.1016/j.imlet.2008.05.007
  3. Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995; 172: 1561-1566. https://doi.org/10.1093/infdis/172.6.1561
  4. Lee SH, Kang HJ, Lee DH, Quan FS. Protective immunity induced by incorporating multiple antigenic proteins of Toxoplasma gondii into influenza virus-like particles. Front Immunol 2019; 9: 3073. https://doi.org/10.3389/fimmu.2018.03073
  5. Hosseininejad M. Evaluation of an indirect ELISA using a tachyzoite surface antigen SAG1 for diagnosis of Toxoplasma gondii infection in cats. Exp Parasitol 2012; 132: 556-560. https://doi.org/10.1016/j.exppara.2012.09.009
  6. Lind P, Haugegaard J, Wingstrand A, Henriksen SA. The time course of the specific antibody response by various ELISAs in pigs experimentally infected with Toxoplasma gondii. Vet Parasitol 1997; 71: 1-15. https://doi.org/10.1016/S0304-4017(97)00010-1
  7. Pishkari S, Shojaee S, Keshavarz H, Salimi M, Mohebali M. Evaluation of Toxoplasma gondii soluble, whole and excretory/secretary antigens for diagnosis of toxoplasmosis by ELISA test. J Parasit Dis 2017; 41: 289-291. https://doi.org/10.1007/s12639-016-0794-1
  8. Sun X, Wang Z, Li J, Wei F, Liu Q. Evaluation of an indirect ELISA using recombinant granule antigen GRA1, GRA7 and soluble antigens for serodiagnosis of Toxoplasma gondii infection in chickens. Res Vet Sci 2015; 100: 161-164. https://doi.org/10.1016/j.rvsc.2015.04.011
  9. Golkar M, Rafati S, Abdel-Latif MS, Brenier-Pinchart M, Fricker-Hidalgo H, Sima BK, Babaie J, Pelloux H, Cesbron-Delauw M, Mercier C. The dense granule protein GRA2, a new marker for the serodiagnosis of acute Toxoplasma infection: comparison of sera collected in both France and Iran from pregnant women. Diagn Microbiol Infect Dis 2007; 58: 419-426. https://doi.org/10.1016/j.diagmicrobio.2007.03.003
  10. Wang Z, Ge W, Huang S, Li J, Zhu X, Liu Q. Evaluation of recombinant granule antigens GRA1 and GRA7 for serodiagnosis of Toxoplasma gondii infection in dogs. BMC Vet Res 2014; 10: 1-6. https://doi.org/10.1186/1746-6148-10-158
  11. Khanaliha K, Motazedian MH, Kazemi B, Shahriari B, Bandehpour M, Sharifniya Z. Evaluation of recombinant SAG1, SAG2, and SAG3 antigens for serodiagnosis of toxoplasmosis. Korean J Parasitol 2014; 52: 137-142. https://doi.org/10.3347/kjp.2014.52.2.137
  12. Ferra B, Holec-Gasior L, Grazlewska W. Toxoplasma gondii recombinant antigens in the serodiagnosis of toxoplasmosis in domestic and farm animals. Animals 2020; 10: 1245. https://doi.org/10.3390/ani10081245
  13. Gatkowska J, Dziadek B, Brzostek A, Dziadek J, Dzitko K, Dlugonska H. Determination of Toxoplasma gondii Recombinant ROP2 and ROP4 Antigens Diagnostic Value on Mouse Experimental Model. Pol J Microbiol 2010; 59: 137-141. https://doi.org/10.33073/pjm-2010-022
  14. Grzybowski MM, Gatkowska JM, Dziadek B, Dzitko K, Dlugonska H. Human toxoplasmosis: a comparative evaluation of the diagnostic potential of recombinant Toxoplasma gondii ROP5 and ROP18 antigens. J Med Microbiol 2015; 64: 1201-1207. https://doi.org/10.1099/jmm.0.000148
  15. Lee SH, Lee DH, Piao Y, Moon EK, Quan FS. Influenza M1 virus-like particles consisting of Toxoplasma gondii rhoptry protein 4. Korean J Parasitol 2017; 55: 143-148. https://doi.org/10.3347/kjp.2017.55.2.143
  16. Kang HJ, Lee SH, Kim MJ, Chu KB, Lee DH, Chopra M, Choi HJ, Park H, Jin H, Quan FS. Influenza virus-like particles presenting both Toxoplasma gondii ROP4 and ROP13 Enhance Protection against T. gondii infection. Pharmaceutics 2019; 11: 342. https://doi.org/10.3390/pharmaceutics11070342
  17. Lee SH, Kim AR, Lee DH, Rubino I, Choi HJ, Quan FSF. Protection induced by virus-like particles containing Toxoplasma gondii microneme protein 8 against highly virulent RH strain of Toxoplasma gondii infection. PLoS One 2017; 12: e0175644. https://doi.org/10.1371/journal.pone.0175644
  18. Drinic M, Wagner A, Sarate P, Zwicker C, Korb E, Loupal G, Peschke R, Joachim A, Wiedermann U, Schabussova I. Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation. Sci Rep 2017; 7: 1-12. https://doi.org/10.1038/s41598-017-15663-4
  19. Kang HJ, Chu KB, Lee DH, Lee SH, Park BR, Kim MC, Kang SM, Quan FS. Influenza M2 virus-like particle vaccination enhances protection in combination with avian influenza HA VLPs. PLoS One 2019; 14: e0216871. https://doi.org/10.1371/journal.pone.0216871
  20. Lee SH, Chu KB, Kang HJ, Quan FS. Virus-like particles containing multiple antigenic proteins of Toxoplasma gondii induce memory T cell and B cell responses. PLoS One 2019; 14: e0220865. https://doi.org/10.1371/journal.pone.0220865
  21. Roozbehani M, Falak R, Mohammadi M, Hemphill A, Razmjou E, reza Meamar A, Masoori L, Khoshmirsafa M, Moradi M, Gharavi MJ. Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii infection. Vaccine 2018; 36: 6124-6132. https://doi.org/10.1016/j.vaccine.2018.08.068
  22. Rahimi MT, Sarvi S, Sharif M, Abediankenari S, Ahmadpour E, Valadan R, Fasihi-Ramandie M, Hosseini S, Daryani A. 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. https://doi.org/10.1007/s00436-016-5325-6
  23. Montoya JG. Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. J Infect Dis 2002; 185 (suppl): 73-82. https://doi.org/10.1086/338827
  24. Elsheikha HM, Marra CM, Zhu XQ. Epidemiology, pathophysiology, diagnosis, and management of cerebral toxoplasmosis. Clin Microbiol Rev 2020; 34: e00115-19. https://doi.org/10.1128/CMR.00115-19
  25. Abdelbaset AE, Alhasan H, Salman D, Karram MH, Rushdi MAE, Xuenan X, Igarashi M. Evaluation of recombinant antigens in combination and single formula for diagnosis of feline toxoplasmosis. Exp Parasitol 2017; 172: 1-4. https://doi.org/10.1016/j.exppara.2016.11.003
  26. Munoz M, Liesenfeld O, Heimesaat MM. Immunology of Toxoplasma gondii. Immunol Rev 2011; 240: 269-285. https://doi.org/10.1111/j.1600-065X.2010.00992.x
  27. Ferra B, Holec-Gasior L, Kur J. Serodiagnosis of Toxoplasma gondii infection in farm animals (horses, swine, and sheep) by enzyme-linked immunosorbent assay using chimeric antigens. Parasitol Int 2015; 64: 288-294. https://doi.org/10.1016/j.parint.2015.03.004
  28. Johnson AM, McDonald PJ, Neoh SH. Kinetics of the growth of Toxoplasma gondii (RH strain) in mice. Int J Parasitol 1979; 9: 55-56. https://doi.org/10.1016/0020-7519(79)90066-3
  29. Holec-Gasior L, Ferra B, Grazlewska W. Toxoplasma gondii tetravalent chimeric proteins as novel antigens for detection of specific immunoglobulin g in sera of small ruminants. Animals 2019; 9: 1146. https://doi.org/10.3390/ani9121146
  30. Villavedra M, Rampoldi C, Carol H, Baz A, Battistoni JJ, Nieto A. Identification of circulating antigens, including an immunoglobulin binding protein, from Toxoplasma gondii tissue cyst and tachyzoites in murine toxoplasmosis. Int J Parasitol 2001; 31: 21-28. https://doi.org/10.1016/S0020-7519(00)00152-1
  31. Kim MJ, Lee SH, Kang HJ, Chu KB, Park H, Jin H, Moon EK, Kim SS, Quan FS. Virus-like particle vaccine displaying Toxoplasma gondii apical membrane antigen 1 induces protection against T. gondii ME49 infection in mice. Microb Pathog 2020; 142: 104090. https://doi.org/10.1016/j.micpath.2020.104090
  32. Lee DH, Lee SH, Kim AR, Quan FS. Virus-like nanoparticle vaccine confers protection against Toxoplasma gondii. PLoS One 2016; 11: e0161231. https://doi.org/10.1371/journal.pone.0161231
  33. Kikuchi T, Furuta T, Kojima S. Kinetics of the nucleoside triphosphate hydrolase of Toxoplasma gondii in mice with acute and chronic toxoplasmosis. Ann Trop Med Parasitol 2002; 96: 35-41. https://doi.org/10.1179/000349802125000493
  34. Picchio MS, Sanchez VR, Arcon N, Soto AS, Perrone Sibilia M, Aldirico MLA, Urrutia M, Moretta R, Fenoy IM, Goldman A, Martin V. Vaccine potential of antigen cocktails composed of recombinant Toxoplasma gondii TgPI-1, ROP2 and GRA4 proteins against chronic toxoplasmosis in C3H mice. Exp Parasitol 2018; 185: 62-70. https://doi.org/10.1016/j.exppara.2018.01.006