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Published in: Medical Microbiology and Immunology 1/2017

01-02-2017 | Original Investigation

Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route

Authors: Imran Rashid, Nathalie Moiré, Bruno Héraut, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec

Published in: Medical Microbiology and Immunology | Issue 1/2017

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Abstract

Infection with the parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. No vaccine is currently available, so the design of efficient vaccine strategies is still a topical question. In this study, we evaluated the immunoprophylactic potential of a T. gondii virulence factor, the rhoptry kinase ROP18, in a mouse model of chronic toxoplasmosis: first using a recombinant protein produced in Schneider insect cells adjuvanted with poly I:C emulsified in Montanide SV71 by a parenteral route or adjuvanted with cholera toxin by the nasal route and second using a DNA plasmid encoding ROP18 adjuvanted with GM-CSF ± IL-12 DNA. If both intranasal and subcutaneous recombinant ROP18 immunizations induced predominantly anti-ROP18 IgG1 antibodies and generated a mixed systemic Th1-/Th2-type cellular immune response characterized by the production of IFN-γ, IL-2, Il-10 and IL-5, only intranasal vaccination induced a mucosal (IgA) humoral response in intestinal washes associated with a significant brain cyst reduction (50 %) after oral challenge with T. gondii cysts. DNA immunization induced antibodies and redirected the cellular immune response toward a Th1-type response (production of IFN-γ and IL-2) but did not confer protection. These results suggest that ROP18 could be a component of a subunit vaccine against toxoplasmosis and that strategies designed to enhance mucosal protective immune responses could lead to more encouraging results.
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Literature
2.
go back to reference Innes EA (2010) Vaccination against Toxoplasma gondii: an increasing priority for collaborative research? Expert Rev Vaccines 9(10):1117–1119CrossRefPubMed Innes EA (2010) Vaccination against Toxoplasma gondii: an increasing priority for collaborative research? Expert Rev Vaccines 9(10):1117–1119CrossRefPubMed
3.
go back to reference Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47(4):554–566CrossRefPubMed Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47(4):554–566CrossRefPubMed
4.
go back to reference Denkers EY, Gazzinelli RT (1998) Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 11(4):569–588PubMedPubMedCentral Denkers EY, Gazzinelli RT (1998) Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 11(4):569–588PubMedPubMedCentral
5.
go back to reference Suzuki Y, Remington J (1990) The effect of anti-IFN-gamma antibody on the protective effect of Lyt-2+ immune T cells against toxoplasmosis in mice. J Immunol 144(5):1954–1960PubMed Suzuki Y, Remington J (1990) The effect of anti-IFN-gamma antibody on the protective effect of Lyt-2+ immune T cells against toxoplasmosis in mice. J Immunol 144(5):1954–1960PubMed
6.
go back to reference Hiszczyńska-Sawicka E, Gatkowska JM, Grzybowski MM, Długońska H (2014) Veterinary vaccines against toxoplasmosis. Parasitology 141(11):1365–1378CrossRefPubMed Hiszczyńska-Sawicka E, Gatkowska JM, Grzybowski MM, Długońska H (2014) Veterinary vaccines against toxoplasmosis. Parasitology 141(11):1365–1378CrossRefPubMed
7.
go back to reference Verma R, Khanna P (2013) Development of Toxoplasma gondii vaccine: a global challenge. Hum Vaccin Immunother 9(2):291–293CrossRefPubMed Verma R, Khanna P (2013) Development of Toxoplasma gondii vaccine: a global challenge. Hum Vaccin Immunother 9(2):291–293CrossRefPubMed
8.
go back to reference Jongert E, Roberts CW, Gargano N, Förster-Waldl E, Petersen E (2009) Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz 104(2):252–266CrossRefPubMed Jongert E, Roberts CW, Gargano N, Förster-Waldl E, Petersen E (2009) Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz 104(2):252–266CrossRefPubMed
9.
go back to reference El Hajj H, Lebrun M, Arold ST, Vial H, Labesse G, Dubremetz JF (2007) ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog 3(2):e14CrossRefPubMedPubMedCentral El Hajj H, Lebrun M, Arold ST, Vial H, Labesse G, Dubremetz JF (2007) ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog 3(2):e14CrossRefPubMedPubMedCentral
10.
go back to reference Etheridge RD, Alaganan A, Tang K, Lou HJ, Turk BE, Sibley LD (2014) The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice. Cell Host Microbe 15(5):537–550CrossRefPubMedPubMedCentral Etheridge RD, Alaganan A, Tang K, Lou HJ, Turk BE, Sibley LD (2014) The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice. Cell Host Microbe 15(5):537–550CrossRefPubMedPubMedCentral
11.
go back to reference Alaganan A, Fentress SJ, Tang K, Wang Q, Sibley LD (2014) Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. Proc Natl Acad Sci USA 111(3):1126–1131CrossRefPubMedPubMedCentral Alaganan A, Fentress SJ, Tang K, Wang Q, Sibley LD (2014) Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. Proc Natl Acad Sci USA 111(3):1126–1131CrossRefPubMedPubMedCentral
12.
go back to reference Bonenfant C, Dimier-Poisson I, Velge-Roussel F, Buzoni-Gatel D, Del Giudice G, Rappuoli R et al (2001) Intranasal immunization with SAG1 and nontoxic mutant heat-labile enterotoxins protects mice against Toxoplasma gondii. Infect Immun 69(3):1605–1612CrossRefPubMedPubMedCentral Bonenfant C, Dimier-Poisson I, Velge-Roussel F, Buzoni-Gatel D, Del Giudice G, Rappuoli R et al (2001) Intranasal immunization with SAG1 and nontoxic mutant heat-labile enterotoxins protects mice against Toxoplasma gondii. Infect Immun 69(3):1605–1612CrossRefPubMedPubMedCentral
13.
go back to reference Debard N, Buzoni-Gatel D, Bout D (1996) Intranasal immunization with SAG1 protein of Toxoplasma gondii in association with cholera toxin dramatically reduces development of cerebral cysts after oral infection. Infect Immun 64(6):2158–2166PubMedPubMedCentral Debard N, Buzoni-Gatel D, Bout D (1996) Intranasal immunization with SAG1 protein of Toxoplasma gondii in association with cholera toxin dramatically reduces development of cerebral cysts after oral infection. Infect Immun 64(6):2158–2166PubMedPubMedCentral
14.
go back to reference Grzybowski MM, Dziadek B, Gatkowska JM, Dzitko K, Długońska H (2015) Towards vaccine against toxoplasmosis: evaluation of the immunogenic and protective activity of recombinant ROP5 and ROP18 Toxoplasma gondii proteins. Parasitol Res 114(12):4553–4563CrossRefPubMed Grzybowski MM, Dziadek B, Gatkowska JM, Dzitko K, Długońska H (2015) Towards vaccine against toxoplasmosis: evaluation of the immunogenic and protective activity of recombinant ROP5 and ROP18 Toxoplasma gondii proteins. Parasitol Res 114(12):4553–4563CrossRefPubMed
15.
go back to reference Aucouturier J, Ascarateil S, Dupuis L (2006) The use of oil adjuvants in therapeutic vaccines. Vaccine 24(Suppl 2):S44–S45CrossRef Aucouturier J, Ascarateil S, Dupuis L (2006) The use of oil adjuvants in therapeutic vaccines. Vaccine 24(Suppl 2):S44–S45CrossRef
16.
go back to reference Liu MA (2011) DNA vaccines: an historical perspective and view to the future. Immunol Rev 239(1):62–84CrossRefPubMed Liu MA (2011) DNA vaccines: an historical perspective and view to the future. Immunol Rev 239(1):62–84CrossRefPubMed
17.
go back to reference Ismael AB, Hedhli D, Cérède O, Lebrun M, Dimier-Poisson I, Mévélec MN (2009) Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii. CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection. Vaccine 27(22):2959–2966CrossRefPubMed Ismael AB, Hedhli D, Cérède O, Lebrun M, Dimier-Poisson I, Mévélec MN (2009) Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii. CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection. Vaccine 27(22):2959–2966CrossRefPubMed
18.
go back to reference Mévélec MN, Bout D, Desolme B, Marchand H, Magne R, Bruneel O et al (2005) Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice. Vaccine 23(36):4489–4499CrossRefPubMed Mévélec MN, Bout D, Desolme B, Marchand H, Magne R, Bruneel O et al (2005) Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice. Vaccine 23(36):4489–4499CrossRefPubMed
19.
go back to reference Xue M, He S, Zhang J, Cui Y, Yao Y, Wang H (2008) Comparison of cholera toxin A2/B and murine interleukin-12 as adjuvants of Toxoplasma multi-antigenic SAG1-ROP2 DNA vaccine. Exp Parasitol 119(3):352–357CrossRefPubMed Xue M, He S, Zhang J, Cui Y, Yao Y, Wang H (2008) Comparison of cholera toxin A2/B and murine interleukin-12 as adjuvants of Toxoplasma multi-antigenic SAG1-ROP2 DNA vaccine. Exp Parasitol 119(3):352–357CrossRefPubMed
20.
go back to reference Cui YL, He SY, Xue MF, Zhang J, Wang HX, Yao Y (2008) Protective effect of a multiantigenic DNA vaccine against Toxoplasma gondii with co-delivery of IL-12 in mice. Parasite Immunol 30(5):309–313CrossRefPubMed Cui YL, He SY, Xue MF, Zhang J, Wang HX, Yao Y (2008) Protective effect of a multiantigenic DNA vaccine against Toxoplasma gondii with co-delivery of IL-12 in mice. Parasite Immunol 30(5):309–313CrossRefPubMed
21.
go back to reference Zhang J, He S, Jiang H, Yang T, Cong H, Zhou H et al (2007) Evaluation of the immune response induced by multiantigenic DNA vaccine encoding SAG1 and ROP2 of Toxoplasma gondii and the adjuvant properties of murine interleukin-12 plasmid in BALB/c mice. Parasitol Res 101(2):331–338CrossRefPubMed Zhang J, He S, Jiang H, Yang T, Cong H, Zhou H et al (2007) Evaluation of the immune response induced by multiantigenic DNA vaccine encoding SAG1 and ROP2 of Toxoplasma gondii and the adjuvant properties of murine interleukin-12 plasmid in BALB/c mice. Parasitol Res 101(2):331–338CrossRefPubMed
22.
go back to reference Letscher-Bru V, Villard O, Risse B, Zauke M, Klein JP, Kien TT (1998) Protective effect of vaccination with a combination of recombinant surface antigen 1 and interleukin-12 against toxoplasmosis in mice. Infect Immun 66(9):4503–4506PubMedPubMedCentral Letscher-Bru V, Villard O, Risse B, Zauke M, Klein JP, Kien TT (1998) Protective effect of vaccination with a combination of recombinant surface antigen 1 and interleukin-12 against toxoplasmosis in mice. Infect Immun 66(9):4503–4506PubMedPubMedCentral
23.
go back to reference Khaznadji E, Boulard C, Moiré N (2003) Expression of functional hypodermin A, a serine protease from Hypoderma lineatum (Diptera, Oestridae), in Schneider 2 cells. Exp Parasitol 104(1–2):33–39CrossRefPubMed Khaznadji E, Boulard C, Moiré N (2003) Expression of functional hypodermin A, a serine protease from Hypoderma lineatum (Diptera, Oestridae), in Schneider 2 cells. Exp Parasitol 104(1–2):33–39CrossRefPubMed
24.
go back to reference Ismael AB, Sekkai D, Collin C, Bout D, Mévélec MN (2003) The MIC3 gene of Toxoplasma gondii is a novel potent vaccine candidate against toxoplasmosis. Infect Immun 71(11):6222–6228CrossRefPubMedPubMedCentral Ismael AB, Sekkai D, Collin C, Bout D, Mévélec MN (2003) The MIC3 gene of Toxoplasma gondii is a novel potent vaccine candidate against toxoplasmosis. Infect Immun 71(11):6222–6228CrossRefPubMedPubMedCentral
25.
go back to reference Jongert E, Lemiere A, Van Ginderachter J, De Craeye S, Huygen K, D’Souza S (2010) Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute Toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine 28(13):2556–2564CrossRefPubMed Jongert E, Lemiere A, Van Ginderachter J, De Craeye S, Huygen K, D’Souza S (2010) Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute Toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine 28(13):2556–2564CrossRefPubMed
26.
go back to reference Akbar H, Germon S, Berthon P, Dimier-Poisson I, Moiré N (2012) Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice. Mem Inst Oswaldo Cruz 107(2):155–162CrossRefPubMed Akbar H, Germon S, Berthon P, Dimier-Poisson I, Moiré N (2012) Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice. Mem Inst Oswaldo Cruz 107(2):155–162CrossRefPubMed
27.
go back to reference Li XZ, Wang XH, Xia LJ, Weng YB, Hernandez JA, Tu LQ et al (2015) Protective efficacy of recombinant canine adenovirus type-2 expressing TgROP18 (CAV-2-ROP18) against acute and chronic Toxoplasma gondii infection in mice. BMC Infect Dis 15:114CrossRefPubMedPubMedCentral Li XZ, Wang XH, Xia LJ, Weng YB, Hernandez JA, Tu LQ et al (2015) Protective efficacy of recombinant canine adenovirus type-2 expressing TgROP18 (CAV-2-ROP18) against acute and chronic Toxoplasma gondii infection in mice. BMC Infect Dis 15:114CrossRefPubMedPubMedCentral
28.
go back to reference Yuan ZG, Zhang XX, Lin RQ, Petersen E, He S, Yu M, He XH, Zhou DH, He Y, Li HX, Liao M, Zhu XQ (2011) Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18. Vaccine 29(38):6614–6619CrossRefPubMed Yuan ZG, Zhang XX, Lin RQ, Petersen E, He S, Yu M, He XH, Zhou DH, He Y, Li HX, Liao M, Zhu XQ (2011) Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18. Vaccine 29(38):6614–6619CrossRefPubMed
29.
go back to reference Appaiahgari MB, Vrati S (2015) Adenoviruses as gene/vaccine delivery vectors: promises and pitfalls. Expert Opin Biol Ther 15(3):337–351CrossRefPubMed Appaiahgari MB, Vrati S (2015) Adenoviruses as gene/vaccine delivery vectors: promises and pitfalls. Expert Opin Biol Ther 15(3):337–351CrossRefPubMed
30.
go back to reference Buus S, Lauemoller SL, Worning P, Kesmir C, Frimurer T, Corbet S et al (2003) Sensitive quantitative predictions of peptide-MHC binding by a ‘Query by Committee’ artificial neural network approach. Tissue Antigens 62(5):378–384CrossRefPubMed Buus S, Lauemoller SL, Worning P, Kesmir C, Frimurer T, Corbet S et al (2003) Sensitive quantitative predictions of peptide-MHC binding by a ‘Query by Committee’ artificial neural network approach. Tissue Antigens 62(5):378–384CrossRefPubMed
31.
go back to reference Nielsen M, Lundegaard C, Worning P, Lauemoller SL, Lamberth K, Buus S et al (2003) Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Sci 12(5):1007–1017CrossRefPubMedPubMedCentral Nielsen M, Lundegaard C, Worning P, Lauemoller SL, Lamberth K, Buus S et al (2003) Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Sci 12(5):1007–1017CrossRefPubMedPubMedCentral
32.
go back to reference Orr MT, Beebe EA, Hudson TE, Argilla D, Huang PW, Reese VA et al (2015) Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy. Vaccine 33(48):6570–6578CrossRefPubMedPubMedCentral Orr MT, Beebe EA, Hudson TE, Argilla D, Huang PW, Reese VA et al (2015) Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy. Vaccine 33(48):6570–6578CrossRefPubMedPubMedCentral
33.
go back to reference McKay PF, King DF, Mann JF, Barinaga G, Carter D, Shattock RJ (2016) TLR4 and TLR7/8 adjuvant combinations generate different vaccine antigen-specific immune outcomes in minipigs when administered via the ID or IN routes. PLoS ONE 11(2):e0148984CrossRefPubMedPubMedCentral McKay PF, King DF, Mann JF, Barinaga G, Carter D, Shattock RJ (2016) TLR4 and TLR7/8 adjuvant combinations generate different vaccine antigen-specific immune outcomes in minipigs when administered via the ID or IN routes. PLoS ONE 11(2):e0148984CrossRefPubMedPubMedCentral
34.
go back to reference Dimier-Poisson I, Carpentier R, N’Guyen TT, Dahmani F, Ducournau C, Betbeder D (2015) Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection. Biomaterials 50:164–175CrossRefPubMed Dimier-Poisson I, Carpentier R, N’Guyen TT, Dahmani F, Ducournau C, Betbeder D (2015) Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection. Biomaterials 50:164–175CrossRefPubMed
Metadata
Title
Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route
Authors
Imran Rashid
Nathalie Moiré
Bruno Héraut
Isabelle Dimier-Poisson
Marie-Noëlle Mévélec
Publication date
01-02-2017
Publisher
Springer Berlin Heidelberg
Published in
Medical Microbiology and Immunology / Issue 1/2017
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-016-0483-9

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