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The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

Abstract

Toxoplasmosis may pose a serious threat for individuals with weakened or undeveloped immune systems. However, to date, there is no specific immunoprophylaxis for humans. Thus, the aim of this study was to evaluate the immunogenicity of three trivalent—SAG2-GRA1-ROP1L (SGR), SAG1L-MIC1-MAG1 (SMM), and GRA1-GRA2-GRA6 (GGG)—and two tetravalent—SAG2-GRA1-ROP1-GRA2 (SGRG) and SAG1-MIC1-MAG1-GRA2 (SMMG)—chimeric T. gondii proteins, as well as their protective potential against chronic toxoplasmosis in laboratory mice. All three trivalent recombinant proteins possessed immunogenic properties, as defined by specific humoral and cellular responses in vaccinated mice characterized by the synthesis of specific IgG (IgG1/IgG2a) antibodies in vivo and the release of Th1/Th2 cytokines by stimulated splenocytes in vitro. Immunization with all three recombinant proteins provided partial protection against toxoplasmosis, although the protective capacity strongly depended on the individual antigenic composition of each preparation. The antigens providing the highest (86%) and lowest (45%) protection, SGR and SMM, respectively, were supplemented with GRA2 antigen fragment, to form the tetravalent chimeric proteins SGRG and SMMG. Further study revealed that the tetravalent preparations exhibited high immunogenic potential; however, the addition of another antigen to the recombinant protein structure had distinct effects on the protection generated, compared to that of the trivalent counterparts, depending on the antigen tested.

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Category:
Articles
Type:
artykuły w czasopismach
Published in:
Vaccines no. 7, pages 1 - 17,
ISSN: 2076-393X
Language:
English
Publication year:
2019
Bibliographic description:
Gatkowska J., Dzitko K., Ferra B., Holec-Gąsior L., Kawka M., Dziadek B.: The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice// Vaccines -Vol. 7,iss. 4 (2019), s.1-17
DOI:
Digital Object Identifier (open in new tab) 10.3390/vaccines7040154
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  1. Buxton, D. Toxoplasmosis: The first commercial vaccine. Parasitol Today 1993, 9, 335-337. [CrossRef] open in new tab
  2. Buxton, D.; Thomson, K.M.; Maley, S.; Wright, S.; Bos, H.J. Experimental challenge of sheep 18 months after vaccination with a live (S48) Toxoplasma gondii vaccine. Vet. Rec. 1993, 133, 310-312. [CrossRef] [PubMed] open in new tab
  3. Innes, E.A.; Bartley, P.M.; Maley, S.; Katzer, F.; Buxton, D. Veterinary vaccines against Toxoplasma gondii. Memórias Inst. Oswaldo Cruz 2009, 104, 246-251. [CrossRef] [PubMed] open in new tab
  4. Jongert, E.; Roberts, C.W.; Gargano, N.; Förster-Waldl, E.; Petersen, E. Vaccines against Toxoplasma gondii: Challenges and opportunities. Memórias Inst. Oswaldo Cruz 2009, 104, 252-266. [CrossRef] open in new tab
  5. Katzer, F.; Canton, G.; Burrells, A.; Palarea-Albaladejo, J.; Horton, B.; Bartley, P.M.; Pang, Y.; Chianini, F.; Innes, E.A.; Benavides, J. Immunization of lambs with the S48 strain of Toxoplasma gondii reduces tissue cyst burden following oral challenge with a complete strain of the parasite. Vet. Parasitol. 2014, 205, 46-56. [CrossRef] open in new tab
  6. Flegr, J. How and why Toxoplasma makes us crazy. Trends Parasitol. 2013, 29, 156-163. [CrossRef] open in new tab
  7. Hsu, P.C.; Groer, M.; Beckie, T. New findings: Depression, suicide, and Toxoplasma gondii infection. J. Am. Assoc. Nurse Pract. 2014, 26, 629-637. [CrossRef] open in new tab
  8. Gulinello, M.; Acquarone, M.; Kim, J.H.; Spray, D.C.; Barbosa, H.S.; Sellers, R.; Tanowitz, H.B.; Weiss, L.M. Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect. 2010, 12, 528-537. [CrossRef] open in new tab
  9. Kamerkar, S.; Davis, P.H. Toxoplasma on the brain: Understanding host-pathogen interactions in chronic CNS infection. J. Parasitol. Res. 2012, 589295. open in new tab
  10. Flegr, J. Effects of Toxoplasma on human behavior. Schizophr. Bull. 2007, 33, 757-760. [CrossRef] open in new tab
  11. Hill, D.; Dubey, J.P. Toxoplasma gondii: Transmission, diagnosis and prevention. Clin. Microbiol. Infect. 2002, 8, 634-640. [CrossRef] [PubMed] open in new tab
  12. Innes, E.A. A brief history and overview of Toxoplasma gondii. Zoonoses Public Health 2010, 57, 1-7. [CrossRef] [PubMed] open in new tab
  13. Ferra, B.; Holec-Gąsior, 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. [CrossRef] [PubMed] open in new tab
  14. Ferra, B.; Holec-Gąsior, L.; Kur, J. A new Toxoplasma gondii chimeric antigen containing fragments of SAG2, GRA1, and ROP1 proteins-impact of immunodominant sequences size on its diagnostic usefulness. Parasitol. Res. 2015, 114, 3291-3299. [CrossRef] [PubMed] open in new tab
  15. Gatkowska, J.; Hiszczynska-Sawicka, E.; Kur, J.; Holec, L.; Dlugonska, H. Toxoplasma gondii: An evaluation of diagnostic value of recombinant antigens in a murine model. Exp. Parasitol. 2006, 114, 220-227. [CrossRef] [PubMed] open in new tab
  16. Dziadek, B.; Gatkowska, J.; Brzostek, A.; Dziadek, J.; Dzitko, K.; Dlugonska, H. Toxoplasma gondii: The immunogenic and protective efficacy of recombinant ROP2 and ROP4 rhoptry proteins in murine experimental toxoplasmosis. Exp. Parasitol. 2009, 123, 81-89. [CrossRef] open in new tab
  17. Holec-Gasior, L.; Kur, J.; Hiszczyńska-Sawicka, E. GRA2 and ROP1 recombinant antigens as potential markers for detection of Toxoplasma gondii-specific immunoglobulin G in humans with acute toxoplasmosis. Clin. Vaccine Immunol. 2009, 16, 510-514. [CrossRef] open in new tab
  18. Holec-Gąsior, L.; Ferra, B.; Drapała, D.; Lautenbach, D.; Kur, J. A new MIC1-MAG1 recombinant chimeric antigen can be used instead of the Toxoplasma gondii lysate antigen in serodiagnosis of human toxoplasmosis. Clin. Vaccine Immunol. 2012, 19, 57-63. [CrossRef] open in new tab
  19. Dziadek, B.; Gatkowska, J.; Brzostek, A.; Dziadek, J.; Dzitko, K.; Grzybowski, M.; Dlugonska, H. Evaluation of three recombinant multi-antigenic vaccines composed of surface and secretory antigens of Toxoplasma gondii in murine models of experimental toxoplasmosis. Vaccine 2011, 29, 821-830. [CrossRef] open in new tab
  20. Gatkowska, J.; Wieczorek, M.; Dziadek, B.; Dzitko, K.; Dziadek, J.; Długońska, H. Assessment of the antigenic and neuroprotective activity of the subunit anti-Toxoplasma vaccine in T. gondii experimentally infected mice. Vet. Parasitol. 2018, 254, 82-94. [CrossRef] open in new tab
  21. Foroutan, M.; Ghaffarifar, F.; Sharifi, Z.; Dalimi, A.; Jorjani, O. Rhoptry antigens as Toxoplasma gondii vaccine target. Clin. Exp. Vaccine Res. 2019, 8, 4-26. [CrossRef] [PubMed] open in new tab
  22. Gatkowska, J.; Gasior, A.; Kur, J.; Dlugonska, H. Toxoplasma gondii: Chimeric Dr fimbriae as a recombinant vaccine against toxoplasmosis. Exp. Parasitol. 2008, 118, 266-270. [CrossRef] [PubMed] open in new tab
  23. Costa-Silva, T.A.; Borges, M.M.; Galhardo, C.S.; Pereira-Chioccola, V.L. Immunization with excreted/secreted proteins in AS/n mice activating cellular and humoral response against Toxoplasma gondii infection. Acta Trop. 2012, 124, 203-209. [CrossRef] [PubMed] open in new tab
  24. Wang, Y.; Zhang, D.; Wang, G.; Yin, H.; Wang, M. Immunization with excreted-secreted antigens reduces tissue cyst formation in pigs. Parasitol. Res. 2013, 112, 3835-3842. [CrossRef] [PubMed] open in new tab
  25. Wagner, A.; Schabussova, I.; Ruttkowski, B.; Peschke, R.; Kur, J.; Kundi, M.; Joachim, A.; Wiedermann, U. Prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in BALB/c mice. PLoS ONE 2015, 10, e0126334. [CrossRef] open in new tab
  26. Allahyari, M.; Mohabati, R.; Amiri, S.; Esmaeili Rastaghi, A.R.; Babaie, J.; Mahdavi, M.; Vatanara, A.; Golkar, M. Synergistic effect of rSAG1 and rGRA2 antigens formulated in PLGA microspheres in eliciting immune protection against Toxoplasama gondii. Exp. Parasitol. 2016, 170, 236-246. [CrossRef] open in new tab
  27. Wang, Y.; Yin, H. Research progress on surface antigen 1 (SAG1) of Toxoplasma gondii. Parasit. Vectors 2014, 7, 180. [CrossRef] open in new tab
  28. Ferguson, D.J.; Parmley, S.F. Toxoplasma gondii MAG1 protein expression. Trends Parasitol. 2002, 18, 482. [CrossRef] open in new tab
  29. Lourenco, E.V.; Bernardes, E.S.; Silva, N.M.; Mineo, J.R.; Panunto-Castelo, A.; Roque-Barreira, M.C. Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma gondii. Microbes Infect. 2006, 8, 1244-1251. [CrossRef] open in new tab
  30. Pinzan, C.F.; Sardinha-Silva, A.; Almeida, F.; Lai, L.; Lopes, C.D.; Lourenço, E.V.; Panunto-Castelo, A.; Matthews, S.; Roque-Barreira, M.C. Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice. PLoS ONE 2015, 10, e0143087. [CrossRef] open in new tab
  31. Scheiblhofer, S.; Laimer, J.; Machado, Y.; Weiss, R.; Thalhamer, J. Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert Rev. Vaccines 2017, 16, 479-489. [CrossRef] [PubMed] open in new tab
  32. Letscher-Bru, V.; Villard, O.; Risse, B.; Zauke, M.; Klein, J.P.; Kien, T.T. Protective effect of vaccination with a combination of recombinant surface antigen 1 and interleukin-12 against toxoplasmosis in mice. Infect. Immun. 1998, 66, 4503-4506. [PubMed] open in new tab
  33. Nielsen, H.V.; Di Cristina, M.; Beghetto, E.; Spadoni, A.; Petersen, E.; Gargano, N. Toxoplasma gondii: DNA vaccination with bradyzoite antigens induces protective immunity in mice against oral infection with parasite cysts. Exp. Parasitol. 2006, 112, 274-279. [CrossRef] [PubMed] open in new tab
  34. Parmley, S.; Slifer, T.; Araujo, F. Protective effects of immunization with a recombinant cyst antigen in mouse models of infection with Toxoplasma gondii tissue cysts. J. Infect. Dis. 2002, 185, S90-S95. [CrossRef] [PubMed] open in new tab
  35. Sonaimuthu, P.; Ching, X.T.; Fong, M.Y.; Kalyanasundaram, R.; Lau, Y.L. Induction of Protective Immunity against Toxoplasmosis in BALB/c Mice Vaccinated with Toxoplasma gondii Rhoptry-1. Front. Microbiol. 2016, 7, 808. [CrossRef] open in new tab
  36. Beghetto, E.; Nielsen, H.V.; Del Porto, P.; Buffolano, W.; Guglietta, S.; Felici, F.; Petersen, E.; Gargano, N. A combination of antigenic regions of Toxoplasma gondii microneme proteins induces protective immunity against oral infection with parasite cysts. J. Infect. Dis. 2005, 191, 637-645. [CrossRef] open in new tab
  37. Golkar, M.; Shokrgozar, M.A.; Rafati, S.; Musset, K.; Assmar, M.; Sadaie, R.; Cesbron-Delauw, M.F.; Mercier, C. Evaluation of protective effect of recombinant dense granule antigens GRA2 and GRA6 formulated in monophosphoryl lipid A (MPL) adjuvant against Toxoplasma chronic infection in mice. Vaccine 2007, 25, 4301-4311. [CrossRef] open in new tab
  38. Bastos, L.M.; Macêdo, A.G., Jr.; Silva, M.V.; Santiago, F.M.; Ramos, E.L.; Santos, F.A.; Pirovani, C.P.; Goulart, L.R.; Mineo, T.W.; Mineo, J.R. Toxoplasma gondii-Derived Synthetic Peptides Containing B-and T-Cell Epitopes from GRA2 Protein Are Able to Enhance Mice Survival in a Model of Experimental Toxoplasmosis. Front. Cell. Infect. Microbiol. 2016, 6, 59. [CrossRef] open in new tab
  39. Carruthers, V.B.; Suzuki, Y. Effects of Toxoplasma gondii infection on the brain. Schizophr. Bull. 2007, 33, 745-751. [CrossRef] open in new tab
  40. Gazzinelli, R.T.; Wysocka, M.; Hieny, S.; Scharton-Kersten, T.; Cheever, A.; Kühn, R.; Müller, W.; Trinchieri, G.; Sher, A. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J. Immunol. 1996, 157, 798-805.
  41. Roers, A.; Siewe, L.; Strittmatter, E.; Deckert, M.; Schlüter, D.; Stenzel, W.; Gruber, A.D.; Krieg, T.; Rajewsky, K.; Müller, W. T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J. Exp. Med. 2004, 200, 1289-1297. [CrossRef] [PubMed] open in new tab
  42. Rosenberg, C.; De Craeye, S.; Jongert, E.; Gargano, N.; Beghetto, E.; Del Porto, P.; Vorup-Jensen, T.; Petersen, E. Induction of partial protection against infection with Toxoplasma gondii genotype II by DNA vaccination with recombinant chimeric tachyzoite antigens. Vaccine 2009, 27, 2489-2498. [CrossRef] [PubMed] open in new tab
  43. Grzybowski, M.M.; Dziadek, B.; Gatkowska, J.M.; Dzitko, K.; Długońska, H. Towards vaccine against toxoplasmosis: Evaluation of the immunogenic and protective activity of recombinant ROP5 and ROP18 Toxoplasma gondii proteins. Parasitol. Res. 2015, 114, 4553-4563. [CrossRef] [PubMed] open in new tab
  44. Yang, C.D.; Chang, G.N.; Chao, D. Protective immunity against Toxoplasma gondii in mice induced by a chimeric protein rSAG1/2. Parasitol. Res. 2004, 92, 58-64. [CrossRef] [PubMed] open in new tab
  45. Chuang, S.C.; Chung, Y.C.; Yang, C.D. Protective immunity against toxoplasmosis in mice induced by single-dose immunization with rSAG1/2 protein released from poly(lactide-co-glycolide) microparticles. Parasite 2017, 24, 5. [CrossRef] [PubMed] open in new tab
  46. Liu, S.; Shi, L.; Cheng, Y.B.; Fan, G.X.; Ren, H.X.; Yuan, Y.K. Evaluation of protective effect of multi-epitope DNA vaccine encoding six antigen segments of Toxoplasma gondii in mice. Parasitol. Res. 2009, 105, 267-274. [CrossRef] open in new tab
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Gdańsk University of Technology

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