Clin Exp Vaccine Res.  2019 Jan;8(1):4-26. 10.7774/cevr.2019.8.1.4.

Rhoptry antigens as Toxoplasma gondii vaccine target

Affiliations
  • 1Abadan School of Medical Sciences, Abadan, Iran.
  • 2Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. ghafarif@modares.ac.ir
  • 3Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
  • 4Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Abstract

Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world's population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%-30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROP-based vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.

Keyword

Toxoplasma gondii; Mice; Vaccines; Immunization; Adjuvant

MeSH Terms

Animals
Antigens, Surface
Apicomplexa
Cell Size
Epitopes
Humans
Immunization
Life Cycle Stages
Mice
Molecular Biology
Mothers
Parasites
Prognosis
Toxoplasma*
Toxoplasmosis
Vaccines
Vaccines, DNA
Vaccines, Synthetic
Zoonoses
Antigens, Surface
Epitopes
Vaccines
Vaccines, DNA
Vaccines, Synthetic

Reference

1. Dubey JP. The history of Toxoplasma gondii: the first 100 years. J Eukaryot Microbiol. 2008; 55:467–475. PMID: 19120791.
2. Rostami A, Riahi SM, Fakhri Y, et al. The global seroprevalence of Toxoplasma gondii among wild boars: a systematic review and meta-analysis. Vet Parasitol. 2017; 244:12–20. PMID: 28917302.
Article
3. Foroutan M, Dalvand S, Daryani A, et al. Rolling up the pieces of a puzzle: a systematic review and meta-analysis of the prevalence of toxoplasmosis in Iran. Alex J Med. 2018; 54:189–196.
Article
4. Nasiri V, Teymurzadeh S, Karimi G, Nasiri M. Molecular detection of Toxoplasma gondii in snakes. Exp Parasitol. 2016; 169:102–106. PMID: 27522027.
Article
5. Khademvatan S, Foroutan M, Hazrati-Tappeh K, et al. Toxoplasmosis in rodents: a systematic review and meta-analysis in Iran. J Infect Public Health. 2017; 10:487–493. PMID: 28237696.
Article
6. Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016; 40:1586–1589. PMID: 27876989.
Article
7. Foroutan-Rad M, Khademvatan S, Majidiani H, Aryamand S, Rahim F, Malehi AS. Seroprevalence of Toxoplasma gondii in the Iranian pregnant women: a systematic review and meta-analysis. Acta Trop. 2016; 158:160–169. PMID: 26952970.
8. Foroutan M, Rostami A, Majidiani H, et al. A systematic review and meta-analysis of the prevalence of toxoplasmosis in hemodialysis patients in Iran. Epidemiol Health. 2018; 40:e2018016. PMID: 29748456.
Article
9. Majidiani H, Dalvand S, Daryani A, Galvan-Ramirez ML, Foroutan-Rad M. Is chronic toxoplasmosis a risk factor for diabetes mellitus? A systematic review and meta-analysis of case-control studies. Braz J Infect Dis. 2016; 20:605–609. PMID: 27768900.
Article
10. Yousefi E, Foroutan M, Salehi R, Khademvatan S. Detection of acute and chronic toxoplasmosis amongst multi-transfused thalassemia patients in southwest of Iran. J Acute Dis. 2017; 6:120–125.
Article
11. Foroutan-Rad M, Majidiani H, Dalvand S, et al. Toxoplasmosis in blood donors: a systematic review and meta-analysis. Transfus Med Rev. 2016; 30:116–122. PMID: 27145927.
Article
12. Wang ZD, Liu HH, Ma ZX, et al. Toxoplasma gondii infection in immunocompromised patients: a systematic review and meta-analysis. Front Microbiol. 2017; 8:389. PMID: 28337191.
Article
13. Foroutan M, Majidiani H. Toxoplasma gondii: are there any implications for routine blood screening? Int J Infect. 2018; 5:e62886.
Article
14. Belluco S, Mancin M, Conficoni D, Simonato G, Pietrobelli M, Ricci A. Investigating the determinants of Toxoplasma gondii prevalence in meat: a systematic review and meta-regression. PLoS One. 2016; 11:e0153856. PMID: 27082633.
Article
15. Kijlstra A, Jongert E. Toxoplasma-safe meat: close to reality? Trends Parasitol. 2009; 25:18–22. PMID: 18951847.
Article
16. Fallahi S, Rostami A, Nourollahpour Shiadeh M, Behniafar H, Paktinat S. An updated literature review on maternal-fetal and reproductive disorders of Toxoplasma gondii infection. J Gynecol Obstet Hum Reprod. 2018; 47:133–140. PMID: 29229361.
Article
17. Antczak M, Dzitko K, Dlugonska H. Human toxoplasmosis-Searching for novel chemotherapeutics. Biomed Pharmacother. 2016; 82:677–684. PMID: 27470411.
Article
18. Buxton D. Toxoplasmosis: the first commercial vaccine. Parasitol Today. 1993; 9:335–337. PMID: 15463799.
Article
19. Zhang NZ, Chen J, Wang M, Petersen E, Zhu XQ. Vaccines against Toxoplasma gondii: new developments and perspectives. Expert Rev Vaccines. 2013; 12:1287–1299. PMID: 24093877.
20. Hiszczynska-Sawicka E, Gatkowska JM, Grzybowski MM, Dlugonska H. Veterinary vaccines against toxoplasmosis. Parasitology. 2014; 141:1365–1378. PMID: 24805159.
Article
21. Garcia JL. Vaccination concepts against Toxoplasma gondii. Expert Rev Vaccines. 2009; 8:215–225. PMID: 19196201.
22. Foroutan M, Ghaffarifar F. Calcium-dependent protein kinases are potential targets for Toxoplasma gondii vaccine. Clin Exp Vaccine Res. 2018; 7:24–36. PMID: 29399577.
23. Camejo A, Gold DA, Lu D, et al. Identification of three novel Toxoplasma gondii rhoptry proteins. Int J Parasitol. 2014; 44:147–160. PMID: 24070999.
Article
24. Dlugonska H. Toxoplasma rhoptries: unique secretory organelles and source of promising vaccine proteins for immunoprevention of toxoplasmosis. J Biomed Biotechnol. 2008; 2008:632424. PMID: 18670609.
25. Bradley PJ, Sibley LD. Rhoptries: an arsenal of secreted virulence factors. Curr Opin Microbiol. 2007; 10:582–587. PMID: 17997128.
Article
26. El Hajj H, Demey E, Poncet J, et al. The ROP2 family of Toxoplasma gondii rhoptry proteins: proteomic and genomic characterization and molecular modeling. Proteomics. 2006; 6:5773–5784. PMID: 17022100.
27. Zhou J, Wang L, Zhou A, et al. Bioinformatics analysis and expression of a novel protein ROP48 in Toxoplasma gondii. Acta Parasitol. 2016; 61:319–328. PMID: 27078655.
Article
28. Reid AJ, Vermont SJ, Cotton JA, et al. Comparative genomics of the apicomplexan parasites Toxoplasma gondii and Neospora caninum: Coccidia differing in host range and transmission strategy. PLoS Pathog. 2012; 8:e1002567. PMID: 22457617.
Article
29. Bradley PJ, Ward C, Cheng SJ, et al. Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in Toxoplasma gondii. J Biol Chem. 2005; 280:34245–34258. PMID: 16002398.
Article
30. Peixoto L, Chen F, Harb OS, et al. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host Microbe. 2010; 8:208–218. PMID: 20709297.
Article
31. Lamarque MH, Papoin J, Finizio AL, et al. Identification of a new rhoptry neck complex RON9/RON10 in the Apicomplexa parasite Toxoplasma gondii. PLoS One. 2012; 7:e32457. PMID: 22427839.
Article
32. El Hajj H, Lebrun M, Fourmaux MN, Vial H, Dubremetz JF. Inverted topology of the Toxoplasma gondii ROP5 rhoptry protein provides new insights into the association of the ROP2 protein family with the parasitophorous vacuole membrane. Cell Microbiol. 2007; 9:54–64. PMID: 16879455.
Article
33. El Hajj H, Lebrun M, Arold ST, Vial H, Labesse G, Dubremetz JF. ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog. 2007; 3:e14. PMID: 17305424.
Article
34. Saeij JP, Boyle JP, Coller S, et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science. 2006; 314:1780–1783. PMID: 17170306.
Article
35. Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: functions and drug targets. Parasitol Res. 2013; 112:2121–2129. PMID: 23681193.
Article
36. Quan JH, Chu JQ, Ismail HA, et al. Induction of protective immune responses by a multiantigenic DNA vaccine encoding GRA7 and ROP1 of Toxoplasma gondii. Clin Vaccine Immunol. 2012; 19:666–674. PMID: 22419676.
Article
37. Bradley PJ, Hsieh CL, Boothroyd JC. Unprocessed Toxoplasma ROP1 is effectively targeted and secreted into the nascent parasitophorous vacuole. Mol Biochem Parasitol. 2002; 125:189–193. PMID: 12467986.
Article
38. Eslamirad Z, Ghaffarifar F, Shojapour M, Khansarinejad B, Sadraei J. A preliminary study: expression of rhoptry protein 1 (ROP1) Toxoplasma gondii in prokaryote system. Jundishapur J Microbiol. 2013; 6:e10089.
Article
39. Saavedra R, Becerril MA, Dubeaux C, et al. Epitopes recognized by human T lymphocytes in the ROP2 protein antigen of Toxoplasma gondii. Infect Immun. 1996; 64:3858–3862. PMID: 8751939.
Article
40. Sinai AP, Joiner KA. The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane. J Cell Biol. 2001; 154:95–108. PMID: 11448993.
Article
41. Saavedra R, de Meuter F, Decourt JL, Herion P. Human T cell clone identifies a potentially protective 54-kDa protein antigen of Toxoplasma gondii cloned and expressed in Escherichia coli. J Immunol. 1991; 147:1975–1982. PMID: 1716289.
42. Liu L, Liu T, Yu L, et al. rROP2(186-533): a novel peptide antigen for detection of IgM antibodies against Toxoplasma gondii. Foodborne Pathog Dis. 2012; 9:7–12. PMID: 22085219.
43. Dziadek B, Dziadek J, Dlugonska H. Identification of Toxoplasma gondii proteins binding human lactoferrin: a new aspect of rhoptry proteins function. Exp Parasitol. 2007; 115:277–282. PMID: 17069806.
Article
44. Khosroshahi KH, Ghaffarifar F, Sharifi Z, Dalimi A. Expression of complete rhoptry protein 2 (ROP2) gene of Toxoplasma gondii in eukaryotic cell. Afr J Biotechnol. 2008; 7:4432–4436.
45. Carey KL, Jongco AM, Kim K, Ward GE. The Toxoplasma gondii rhoptry protein ROP4 is secreted into the parasitophorous vacuole and becomes phosphorylated in infected cells. Eukaryot Cell. 2004; 3:1320–1330. PMID: 15470260.
46. Wang L, Lu G, Zhou A, et al. Evaluation of immune responses induced by rhoptry protein 5 and rhoptry protein 7 DNA vaccines against Toxoplasma gondii. Parasite Immunol. 2016; 38:209–217. PMID: 26802673.
47. Chen J, Li ZY, Petersen E, Huang SY, Zhou DH, Zhu XQ. DNA vaccination with genes encoding Toxoplasma gondii antigens ROP5 and GRA15 induces protective immunity against toxoplasmosis in Kunming mice. Expert Rev Vaccines. 2015; 14:617–624. PMID: 25749394.
48. Zheng B, Lu S, Tong Q, Kong Q, Lou D. The virulence-related rhoptry protein 5 (ROP5) of Toxoplasma gondii is a novel vaccine candidate against toxoplasmosis in mice. Vaccine. 2013; 31:4578–4584. PMID: 23928460.
Article
49. Hajj HE, Lebrun M, Fourmaux MN, Vial H, Dubremetz JF. Characterization, biosynthesis and fate of ROP7, a ROP2 related rhoptry protein of Toxoplasma gondii. Mol Biochem Parasitol. 2006; 146:98–100. PMID: 16330111.
Article
50. Parthasarathy S, Fong MY, Ramaswamy K, Lau YL. Protective immune response in BALB/c mice induced by DNA vaccine of the ROP8 gene of Toxoplasma gondii. Am J Trop Med Hyg. 2013; 88:883–887. PMID: 23509124.
Article
51. Foroutan M, Ghaffarifar F, Sharifi Z, Dalimi A, Pirestani M. Bioinformatics analysis of ROP8 protein to improve vaccine design against Toxoplasma gondii. Infect Genet Evol. 2018; 62:193–204. PMID: 29705360.
Article
52. Chen J, Zhou DH, Li ZY, et al. Toxoplasma gondii: protective immunity induced by rhoptry protein 9 (TgROP9) against acute toxoplasmosis. Exp Parasitol. 2014; 139:42–48. PMID: 24602875.
Article
53. Reichmann G, Dlugonska H, Fischer HG. Characterization of TgROP9 (p36), a novel rhoptry protein of Toxoplasma gondii tachyzoites identified by T cell clone. Mol Biochem Parasitol. 2002; 119:43–54. PMID: 11755185.
Article
54. Wang PY, Yuan ZG, Petersen E, et al. Protective efficacy of a Toxoplasma gondii rhoptry protein 13 plasmid DNA vaccine in mice. Clin Vaccine Immunol. 2012; 19:1916–1920. PMID: 23015648.
Article
55. Turetzky JM, Chu DK, Hajagos BE, Bradley PJ. Processing and secretion of ROP13: A unique Toxoplasma effector protein. Int J Parasitol. 2010; 40:1037–1044. PMID: 20359481.
Article
56. Butcher BA, Fox BA, Rommereim LM, et al. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog. 2011; 7:e1002236. PMID: 21931552.
Article
57. Yuan ZG, Zhang XX, He XH, et al. Protective immunity induced by Toxoplasma gondii rhoptry protein 16 against toxoplasmosis in mice. Clin Vaccine Immunol. 2011; 18:119–124. PMID: 21106780.
58. Saeij JP, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature. 2007; 445:324–327. PMID: 17183270.
Article
59. Cao A, Liu Y, Wang J, et al. Toxoplasma gondii: vaccination with a DNA vaccine encoding T- and B-cell epitopes of SAG1, GRA2, GRA7 and ROP16 elicits protection against acute toxoplasmosis in mice. Vaccine. 2015; 33:6757–6762. PMID: 26518401.
Article
60. Wang HL, Yin LT, Zhang TE, et al. Construction, expression and kinase function analysis of an eukaryocyte vector of rhoptry protein 17 in Toxoplasma gondii. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2014; 32:29–33. PMID: 24822361.
61. Qiu W, Wernimont A, Tang K, et al. Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii. EMBO J. 2009; 28:969–979. PMID: 19197235.
Article
62. Wang HL, Wang YJ, Pei YJ, et al. DNA vaccination with a gene encoding Toxoplasma gondii Rhoptry Protein 17 induces partial protective immunity against lethal challenge in mice. Parasite. 2016; 23:4. PMID: 26842927.
63. Taylor S, Barragan A, Su C, et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science. 2006; 314:1776–1780. PMID: 17170305.
64. Qu D, Han J, Du A. Evaluation of protective effect of multiantigenic DNA vaccine encoding MIC3 and ROP18 antigen segments of Toxoplasma gondii in mice. Parasitol Res. 2013; 112:2593–2599. PMID: 23591483.
Article
65. Fentress SJ, Steinfeldt T, Howard JC, Sibley LD. The arginine-rich N-terminal domain of ROP18 is necessary for vacuole targeting and virulence of Toxoplasma gondii. Cell Microbiol. 2012; 14:1921–1933. PMID: 22906355.
66. Zhou J, Wang L, Lu G, et al. Epitope analysis and protection by a ROP19 DNA vaccine against Toxoplasma gondii. Parasite. 2016; 23:17. PMID: 27055564.
67. Xu Y, Zhang NZ, Tan QD, et al. Evaluation of immuno-efficacy of a novel DNA vaccine encoding Toxoplasma gondii rhoptry protein 38 (TgROP38) against chronic toxoplasmosis in a murine model. BMC Infect Dis. 2014; 14:525. PMID: 25267356.
Article
68. Xu Y, Zhang NZ, Chen J, et al. Toxoplasma gondii rhoptry protein 38 gene: sequence variation among isolates from different hosts and geographical locations. Genet Mol Res. 2014; 13:4839–4844. PMID: 24446336.
Article
69. Yang WB, Zhou DH, Zou Y, et al. Vaccination with a DNA vaccine encoding Toxoplasma gondii ROP54 induces protective immunity against toxoplasmosis in mice. Acta Trop. 2017; 176:427–432. PMID: 28935555.
Article
70. Kim EW, Nadipuram SM, Tetlow AL, et al. The rhoptry pseudokinase ROP54 modulates Toxoplasma gondii virulence and host GBP2 loading. mSphere. 2016; 1:e00045-16.
Article
71. Garcia JL, Innes EA, Katzer F. Current progress toward vaccines against Toxoplasma gondii. Vaccine Devel Ther. 2014; 4:23–37.
Article
72. Pifer R, Yarovinsky F. Innate responses to Toxoplasma gondii in mice and humans. Trends Parasitol. 2011; 27:388–393. PMID: 21550851.
Article
73. Mouse Genome Sequencing Consortium. Waterston RH, Lindblad-Toh K, et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420:520–562. PMID: 12466850.
Article
74. Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004; 172:2731–2738. PMID: 14978070.
Article
75. Dziadek B, Gatkowska J, Grzybowski M, Dziadek J, Dzitko K, Dlugonska H. Toxoplasma gondii: the vaccine potential of three trivalent antigen-cocktails composed of recombinant ROP2, ROP4, GRA4 and SAG1 proteins against chronic toxoplasmosis in BALB/c mice. Exp Parasitol. 2012; 131:133–138. PMID: 22445587.
Article
76. Dziadek B, Gatkowska J, Brzostek A, et al. 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. PMID: 21087690.
Article
77. Echeverria PC, de Miguel N, Costas M, Angel SO. Potent antigen-specific immunity to Toxoplasma gondii in adjuvant-free vaccination system using Rop2-Leishmania infantum Hsp83 fusion protein. Vaccine. 2006; 24:4102–4110. PMID: 16545504.
Article
78. Ghaffarifar F. Strategies of DNA vaccines against toxoplasmosis. Rev Med Microbiol. 2015; 26:88–90.
Article
79. Ghaffarifar F. Plasmid DNA vaccines: where are we now? Drugs Today (Barc). 2018; 54:315–333. PMID: 29911696.
Article
80. Li L, Petrovsky N. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 2016; 15:313–329. PMID: 26707950.
Article
81. Saade F, Petrovsky N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines. 2012; 11:189–209. PMID: 22309668.
Article
82. Zhang NZ, Wang M, Xu Y, Petersen E, Zhu XQ. Recent advances in developing vaccines against Toxoplasma gondii: an update. Expert Rev Vaccines. 2015; 14:1609–1621. PMID: 26467840.
83. Lim SS, Othman RY. Recent advances in Toxoplasma gondii immunotherapeutics. Korean J Parasitol. 2014; 52:581–593. PMID: 25548409.
Article
84. Sayles PC, Gibson GW, Johnson LL. B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii. Infect Immun. 2000; 68:1026–1033. PMID: 10678903.
85. Denkers EY, Gazzinelli RT. Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev. 1998; 11:569–588. PMID: 9767056.
86. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988; 240:516–518. PMID: 3128869.
87. Liu Q, Wang F, Wang G, et al. Toxoplasma gondii: immune response and protective efficacy induced by ROP16/GRA7 multicomponent DNA vaccine with a genetic adjuvant B7-2. Hum Vaccin Immunother. 2014; 10:184–191. PMID: 24096573.
88. Yuan ZG, Zhang XX, Lin RQ, et al. Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18. Vaccine. 2011; 29:6614–6619. PMID: 21762755.
Article
89. Eslamirad Z, Dalimi A, Ghaffarifar F, Sharifi Z, Hosseini AZ. Induction of protective immunity against toxoplasmosis in mice by immunization with a plasmid encoding Toxoplama gondii ROP1 gene. Afr J Biotechnol. 2012; 11:8735–8741.
Article
90. Hoseinian Khosroshahi K, Ghaffarifar F, D'Souza S, Sharifi Z, Dalimi A. Evaluation of the immune response induced by DNA vaccine cocktail expressing complete SAG1 and ROP2 genes against toxoplasmosis. Vaccine. 2011; 29:778–783. PMID: 21095254.
Article
91. Leyva R, Herion P, Saavedra R. Genetic immunization with plasmid DNA coding for the ROP2 protein of Toxoplasma gondii. Parasitol Res. 2001; 87:70–79. PMID: 11199854.
Article
92. Naserifar R, Ghaffarifar F, Dalimi A, Sharifi Z, Solhjoo K, Hosseinian Khosroshahi K. Evaluation of immunogenicity of cocktail DNA vaccine containing plasmids encoding complete GRA5, SAG1, and ROP2 antigens of Toxoplasma gondii in BALB/C mice. Iran J Parasitol. 2015; 10:590–598. PMID: 26811726.
93. Zhang J, He S, Jiang H, et al. 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. 2007; 101:331–338. PMID: 17265053.
Article
94. Cui YL, He SY, Xue MF, Zhang J, Wang HX, Yao Y. Protective effect of a multiantigenic DNA vaccine against Toxoplasma gondii with co-delivery of IL-12 in mice. Parasite Immunol. 2008; 30:309–313. PMID: 18331395.
Article
95. Bureau MF, Naimi S, Torero Ibad R, et al. Intramuscular plasmid DNA electrotransfer: biodistribution and degradation. Biochim Biophys Acta. 2004; 1676:138–148. PMID: 14746908.
96. Greenland JR, Letvin NL. Chemical adjuvants for plasmid DNA vaccines. Vaccine. 2007; 25:3731–3741. PMID: 17350735.
Article
97. Montomoli E, Piccirella S, Khadang B, Mennitto E, Camerini R, De Rosa A. Current adjuvants and new perspectives in vaccine formulation. Expert Rev Vaccines. 2011; 10:1053–1061. PMID: 21806399.
Article
98. Khosroshahi KH, Ghaffarifar F, Sharifi Z, et al. Comparing the effect of IL-12 genetic adjuvant and alum non-genetic adjuvant on the efficiency of the cocktail DNA vaccine containing plasmids encoding SAG-1 and ROP-2 of Toxoplasma gondii. Parasitol Res. 2012; 111:403–411. PMID: 22350714.
Article
99. Xue M, He S, Zhang J, Cui Y, Yao Y, Wang H. Comparison of cholera toxin A2/B and murine interleukin-12 as adjuvants of Toxoplasma multi-antigenic SAG1-ROP2 DNA vaccine. Exp Parasitol. 2008; 119:352–357. PMID: 18442818.
Article
100. Guo H, Chen G, Lu F, Chen H, Zheng H. Immunity induced by DNA vaccine of plasmid encoding the rhoptry protein 1 gene combined with the genetic adjuvant of pcIFN-gamma against Toxoplasma gondii in mice. Chin Med J (Engl). 2001; 114:317–320. PMID: 11780322.
101. Xue M, He S, Cui Y, Yao Y, Wang H. Evaluation of the immune response elicited by multi-antigenic DNA vaccine expressing SAG1, ROP2 and GRA2 against Toxoplasma gondii. Parasitol Int. 2008; 57:424–429. PMID: 18562245.
Article
102. Rashid I, Moire N, Heraut B, Dimier-Poisson I, Mevelec MN. Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route. Med Microbiol Immunol. 2017; 206:53–62. PMID: 27757545.
Article
103. Gazzinelli RT, Wysocka M, Hayashi S, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol. 1994; 153:2533–2543. PMID: 7915739.
104. Hyodo Y, Matsui K, Hayashi N, et al. IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J Immunol. 1999; 162:1662–1668. PMID: 9973427.
105. Zhang T, Kawakami K, Qureshi MH, Okamura H, Kurimoto M, Saito A. Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells. Infect Immun. 1997; 65:3594–3599. PMID: 9284124.
Article
106. Marshall DJ, Rudnick KA, McCarthy SG, et al. Interleukin-18 enhances Th1 immunity and tumor protection of a DNA vaccine. Vaccine. 2006; 24:244–253. PMID: 16135392.
Article
107. Maue AC, Waters WR, Palmer MV, et al. CD80 and CD86, but not CD154, augment DNA vaccine-induced protection in experimental bovine tuberculosis. Vaccine. 2004; 23:769–779. PMID: 15542201.
Article
108. Santra S, Barouch DH, Jackson SS, et al. Functional equivalency of B7-1 and B7-2 for costimulating plasmid DNA vaccine-elicited CTL responses. J Immunol. 2000; 165:6791–6795. PMID: 11120800.
Article
109. Sanchez VR, Pitkowski MN, Fernandez Cuppari AV, et al. Combination of CpG-oligodeoxynucleotides with recombinant ROP2 or GRA4 proteins induces protective immunity against Toxoplasma gondii infection. Exp Parasitol. 2011; 128:448–453. PMID: 21554876.
110. Cong H, Gu QM, Yin HE, et al. Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii. Vaccine. 2008; 26:3913–3921. PMID: 18555564.
Article
111. Hajishengallis G, Hollingshead SK, Koga T, Russell MW. Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits. J Immunol. 1995; 154:4322–4332. PMID: 7722290.
112. Igarashi M, Kano F, Tamekuni K, et al. Toxoplasma gondii: evaluation of an intranasal vaccine using recombinant proteins against brain cyst formation in BALB/c mice. Exp Parasitol. 2008; 118:386–392. PMID: 18154953.
Article
113. Martin V, Supanitsky A, Echeverria PC, et al. Recombinant GRA4 or ROP2 protein combined with alum or the gra4 gene provides partial protection in chronic murine models of toxoplasmosis. Clin Diagn Lab Immunol. 2004; 11:704–710. PMID: 15242945.
114. Nabi H, Rashid I, Ahmad N, et al. Induction of specific humoral immune response in mice immunized with ROP18 nanospheres from Toxoplasma gondii. Parasitol Res. 2017; 116:359–370. PMID: 27785602.
Article
115. Xu Y, Zhang NZ, Wang M, et al. A long-lasting protective immunity against chronic toxoplasmosis in mice induced by recombinant rhoptry proteins encapsulated in poly (lactide-co-glycolide) microparticles. Parasitol Res. 2015; 114:4195–4203. PMID: 26243574.
Article
116. Zhang NZ, Xu Y, Wang M, et al. Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infect Dis. 2016; 16:168. PMID: 27090890.
Article
117. Jain S, O'Hagan DT, Singh M. The long-term potential of biodegradable poly(lactide-co-glycolide) microparticles as the next-generation vaccine adjuvant. Expert Rev Vaccines. 2011; 10:1731–1742. PMID: 22085176.
Article
118. Igarashi M, Zulpo DL, Cunha IA, et al. Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized via intranasal route with rTgROP2. Rev Bras Parasitol Vet. 2010; 19:210–216. PMID: 21184696.
Article
119. Qu D, Han J, Du A. Enhancement of protective immune response to recombinant Toxoplasma gondii ROP18 antigen by ginsenoside Re. Exp Parasitol. 2013; 135:234–239. PMID: 23896123.
Article
120. Li Y, Xie F, Chen J, Fan Q, Zhai L, Hu S. Increased humoral immune responses of pigs to foot-and-mouth disease vaccine supplemented with ginseng stem and leaf saponins. Chem Biodivers. 2012; 9:2225–2235. PMID: 23081923.
Article
121. Yang ZG, Ye YP, Sun HX. Immunological adjuvant effect of ginsenoside Rh4 from the roots of Panax notoginseng on specific antibody and cellular response to ovalbumin in mice. Chem Biodivers. 2007; 4:232–240. PMID: 17311234.
122. Sun J, Hu S, Song X. Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice. Vaccine. 2007; 25:1114–1120. PMID: 17069940.
Article
123. Rivera E, Hu S, Concha C. Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants. Vaccine. 2003; 21:1149–1157. PMID: 12559792.
Article
124. Hu S, Concha C, Lin F, Persson Waller K. Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol. 2003; 91:29–37. PMID: 12507847.
Article
125. Chen H, Chen G, Zheng H, Guo H. Induction of immune responses in mice by vaccination with Liposome-entrapped DNA complexes encoding Toxoplasma gondii SAG1 and ROP1 genes. Chin Med J (Engl). 2003; 116:1561–1566. PMID: 14570624.
126. Jorritsma SHT, Gowans EJ, Grubor-Bauk B, Wijesundara DK. Delivery methods to increase cellular uptake and immunogenicity of DNA vaccines. Vaccine. 2016; 34:5488–5494. PMID: 27742218.
Article
127. Yap G, Pesin M, Sher A. Cutting edge: IL-12 is required for the maintenance of IFN-gamma production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii. J Immunol. 2000; 165:628–631. PMID: 10878333.
128. Agadjanyan MG, Kim JJ, Trivedi N, et al. CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo. J Immunol. 1999; 162:3417–3427. PMID: 10092797.
129. Iwasaki A, Stiernholm BJ, Chan AK, Berinstein NL, Barber BH. Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines. J Immunol. 1997; 158:4591–4601. PMID: 9144471.
130. Wang Y, Wang G, Cai J, Yin H. Review on the identification and role of Toxoplasma gondii antigenic epitopes. Parasitol Res. 2016; 115:459–468. PMID: 26581372.
Article
131. Mbow ML, De Gregorio E, Ulmer JB. Alum's adjuvant action: grease is the word. Nat Med. 2011; 17:415–416. PMID: 21475229.
Article
132. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines. 2011; 10:499–511. PMID: 21506647.
Article
133. Liu S, Shi L, Cheng YB, Fan GX, Ren HX, Yuan YK. Evaluation of protective effect of multi-epitope DNA vaccine encoding six antigen segments of Toxoplasma gondii in mice. Parasitol Res. 2009; 105:267–274. PMID: 19288132.
Article
134. El-Malky M, Shaohong L, Kumagai T, et al. Protective effect of vaccination with Toxoplasma lysate antigen and CpG as an adjuvant against Toxoplasma gondii in susceptible C57BL/6 mice. Microbiol Immunol. 2005; 49:639–646. PMID: 16034207.
135. Spencer JA, Smith BF, Guarino AJ, Blagburn BL, Baker HJ. The use of CpG as an adjuvant to Toxoplasma gondii vaccination. Parasitol Res. 2004; 92:313–316. PMID: 14727185.
Article
136. Saavedra R, Leyva R, Tenorio EP, et al. CpG-containing ODN has a limited role in the protection against Toxoplasma gondii. Parasite Immunol. 2004; 26:67–73. PMID: 15225293.
Article
137. Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release. 2003; 90:261–280. PMID: 12880694.
Article
138. Wang HL, Zhang TE, Yin LT, et al. Partial protective effect of intranasal immunization with recombinant Toxoplasma gondii rhoptry protein 17 against toxoplasmosis in mice. PLoS One. 2014; 9:e108377. PMID: 25255141.
Article
139. Velge-Roussel F, Marcelo P, Lepage AC, Buzoni-Gatel D, Bout DT. Intranasal immunization with Toxoplasma gondii SAG1 induces protective cells into both NALT and GALT compartments. Infect Immun. 2000; 68:969–972. PMID: 10639474.
140. Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol. 2012; 12:592–605. PMID: 22828912.
Article
141. Wu HY, Russell MW. Induction of mucosal and systemic immune responses by intranasal immunization using recombinant cholera toxin B subunit as an adjuvant. Vaccine. 1998; 16:286–292. PMID: 9607044.
Article
142. Romano P, Giugno R, Pulvirenti A. Tools and collaborative environments for bioinformatics research. Brief Bioinform. 2011; 12:549–561. PMID: 21984743.
Article
143. Flower DR, Macdonald IK, Ramakrishnan K, Davies MN, Doytchinova IA. Computer aided selection of candidate vaccine antigens. Immunome Res. 2010; 6(Suppl 2):S1.
Article
144. Zhou J, Lu G, Wang L, et al. Structuraland antigenic analysis of a new rhoptry pseudokinase gene (ROP54) in Toxoplasma gondii. Acta Parasitol. 2017; 62:513–519. PMID: 28682759.
Article
145. Yin H, Zhao L, Wang T, Zhou H, He S, Cong H. A Toxoplasma gondii vaccine encoding multistage antigens in conjunction with ubiquitin confers protective immunity to BALB/c mice against parasite infection. Parasit Vectors. 2015; 8:498. PMID: 26420606.
Article
146. Wang T, Yin H, Li Y, Zhao L, Sun X, Cong H. Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes. Parasite. 2017; 24:12. PMID: 28367800.
147. Cong H, Yuan Q, Zhao Q, et al. Comparative efficacy of a multi-epitope DNA vaccine via intranasal, peroral, and intramuscular delivery against lethal Toxoplasma gondii infection in mice. Parasit Vectors. 2014; 7:145. PMID: 24685150.
Article
148. Alexander J, Jebbari H, Bluethmann H, Satoskar A, Roberts CW. Immunological control of Toxoplasma gondii and appropriate vaccine design. Curr Top Microbiol Immunol. 1996; 219:183–195. PMID: 8791700.
Article
149. Oldenburg M, Kruger A, Ferstl R, et al. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science. 2012; 337:1111–1115. PMID: 22821982.
150. Cong H, Gu QM, Jiang Y, et al. Oral immunization with a live recombinant attenuated Salmonella typhimurium protects mice against Toxoplasma gondii. Parasite Immunol. 2005; 27:29–35. PMID: 15813720.
Article
151. Li XZ, Lv L, Zhang X, et al. Recombinant canine adenovirus type-2 expressing TgROP16 provides partial protection against acute Toxoplasma gondii infection in mice. Infect Genet Evol. 2016; 45:447–453. PMID: 27742446.
Article
152. Li XZ, Wang XH, Xia LJ, et al. 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. 2015; 15:114. PMID: 25886737.
Article
153. Wang H, Liu Q, Liu K, et al. Immune response induced by recombinant Mycobacterium bovis BCG expressing ROP2 gene of Toxoplasma gondii. Parasitol Int. 2007; 56:263–268. PMID: 17587637.
Article
154. Roque-Resendiz JL, Rosales R, Herion P. MVA ROP2 vaccinia virus recombinant as a vaccine candidate for toxoplasmosis. Parasitology. 2004; 128(Pt 4):397–405. PMID: 15151145.
Article
155. Flynn JL. Recombinant BCG as an antigen delivery system. Cell Mol Biol (Noisy-le-grand). 1994; 40(Suppl 1):31–36. PMID: 7950859.
156. Frommel D, Lagrange PH. BCG: a modifier of immune responses to parasites. Parasitol Today. 1989; 5:188–190. PMID: 15463209.
Article
157. Shepard CC, Walker LL, van Landingham R. Heat stability of Mycobacterium leprae immunogenicity. Infect Immun. 1978; 22:87–93. PMID: 365752.
Article
158. Levine AJ. The origins of the small DNA tumor viruses. Adv Cancer Res. 1994; 65:141–168. PMID: 7879664.
Article
159. Yang TC, Millar JB, Grinshtein N, Bassett J, Finn J, Bramson JL. T-cell immunity generated by recombinant adenovirus vaccines. Expert Rev Vaccines. 2007; 6:347–356. PMID: 17542750.
Article
160. Appledorn DM, Patial S, Godbehere S, Parameswaran N, Amalfitano A. TRIF, and TRIF-interacting TLRs differentially modulate several adenovirus vector-induced immune responses. J Innate Immun. 2009; 1:376–388. PMID: 20375595.
Article
161. Appledorn DM, Patial S, McBride A, et al. Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo. J Immunol. 2008; 181:2134–2144. PMID: 18641352.
Article
162. Zak DE, Andersen-Nissen E, Peterson ER, et al. Merck Ad5/HIV induces broad innate immune activation that predicts CD8(+) T-cell responses but is attenuated by preexisting Ad5 immunity. Proc Natl Acad Sci U S A. 2012; 109:E3503–E3512. PMID: 23151505.
Article
163. Paillard F. Advantages of non-human adenoviruses versus human adenoviruses. Hum Gene Ther. 1997; 8:2007–2009. PMID: 9414248.
164. Casciotti L, Ely KH, Williams ME, Khan IA. CD8(+)-T-cell immunity against Toxoplasma gondii can be induced but not maintained in mice lacking conventional CD4(+) T cells. Infect Immun. 2002; 70:434–443. PMID: 11796568.
165. Detmer A, Glenting J. Live bacterial vaccines: a review and identification of potential hazards. Microb Cell Fact. 2006; 5:23. PMID: 16796731.
166. Abdian N, Gholami E, Zahedifard F, Safaee N, Rafati S. Evaluation of DNA/DNA and prime-boost vaccination using LPG3 against Leishmania major infection in susceptible BALB/c mice and its antigenic properties in human leishmaniasis. Exp Parasitol. 2011; 127:627–636. PMID: 21187087.
Article
167. Moore AC, Hill AV. Progress in DNA-based heterologous prime-boost immunization strategies for malaria. Immunol Rev. 2004; 199:126–143. PMID: 15233731.
Article
168. Li WS, Chen QX, Ye JX, Xie ZX, Chen J, Zhang LF. Comparative evaluation of immunization with recombinant protein and plasmid DNA vaccines of fusion antigen ROP2 and SAG1 from Toxoplasma gondii in mice: cellular and humoral immune responses. Parasitol Res. 2011; 109:637–644. PMID: 21404064.
Article
169. Kardani K, Bolhassani A, Shahbazi S. Prime-boost vaccine strategy against viral infections: mechanisms and benefits. Vaccine. 2016; 34:413–423. PMID: 26691569.
Article
170. Chea LS, Amara RR. Immunogenicity and efficacy of DNA/MVA HIV vaccines in rhesus macaque models. Expert Rev Vaccines. 2017; 16:973–985. PMID: 28838267.
Article
171. Ledgerwood JE, Zephir K, Hu Z, et al. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis. 2013; 208:418–422. PMID: 23633407.
Article
172. Lu S. Heterologous prime-boost vaccination. Curr Opin Immunol. 2009; 21:346–351. PMID: 19500964.
Article
173. Chen JH, Yu YS, Liu HH, et al. Ubiquitin conjugation of hepatitis B virus core antigen DNA vaccine leads to enhanced cell-mediated immune response in BALB/c mice. Hepat Mon. 2011; 11:620–628. PMID: 22140385.
Article
174. Schwartz AL, Ciechanover A. The ubiquitin-proteasome pathway and pathogenesis of human diseases. Annu Rev Med. 1999; 50:57–74. PMID: 10073263.
175. Kosinska AD, Johrden L, Zhang E, et al. DNA prime-adenovirus boost immunization induces a vigorous and multifunctional T-cell response against hepadnaviral proteins in the mouse and woodchuck model. J Virol. 2012; 86:9297–9310. PMID: 22718818.
Article
176. Rollier C, Verschoor EJ, Paranhos-Baccala G, et al. Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus macaques by altering priming before adenovirus boosting. J Infect Dis. 2005; 192:920–929. PMID: 16088843.
Article
177. Kibuuka H, Kimutai R, Maboko L, et al. A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172). J Infect Dis. 2010; 201:600–607. PMID: 20078213.
Article
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