Browse > Article
http://dx.doi.org/10.3347/kjp.2017.55.5.505

DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice  

Han, Yali (Department of Parasitology, Shandong University School of Medicine)
Zhou, Aihua (Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Shandong University School of Medicine)
Lu, Gang (Department of Parasitology, Shandong University School of Medicine)
Zhao, Guanghui (Qilu Hospital of Shandong University)
Sha, Wenchao (Department of Parasitology, Shandong University School of Medicine)
Wang, Lin (Department of Jinan Children's Hospital)
Guo, Jingjing (Department of Parasitology, Shandong University School of Medicine)
Zhou, Jian (Department of Parasitology, Shandong University School of Medicine)
Zhou, Huaiyu (Department of Parasitology, Shandong University School of Medicine)
Cong, Hua (Department of Parasitology, Shandong University School of Medicine)
He, Shenyi (Department of Parasitology, Shandong University School of Medicine)
Publication Information
Parasites, Hosts and Diseases / v.55, no.5, 2017 , pp. 505-512 More about this Journal
Abstract
Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant ${\alpha}-GalCer$. As results, TgCPC1 DNA vaccine with or without adjuvant ${\alpha}-GalCer$ showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and $IFN-{\gamma}$ in the spleen compared to controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). Upon challenge infection with tachyzoites of T. gondii (RH), $pCPC1/{\alpha}-GalCer$ immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.
Keywords
Toxoplasma gondii; DNA vaccine; CPC1; protective immunity; mouse;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wang Y, Wang G, Ou J, Yin H, Zhang D. Analyzing and identifying novel B cell epitopes within Toxoplasma gondii GRA4. Parasit Vectors 2014; 7: 474.   DOI
2 Filisetti D, Candolfi E. Immune response to Toxoplasma gondii. Ann Ist Super Sanita 2004; 40: 71-80.
3 El-Kady IM. T-cell immunity in human chronic toxoplasmosis. J Egypt Soc Parasitol 2011; 41: 17-28.
4 Oldenhove G, Bouladoux N, Wohlfert EA, Hall JA, Chou D, Dos Santos L, O'Brien S, Blank R, Lamb E, Natarajan S, Kastenmayer R, Hunter C, Grigg ME, Belkaid Y. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 2009; 31: 772-786.   DOI
5 Sayles PC, Gibson GW, Johnson LL. B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii. Infect Immun 2000; 68: 1026-1033.   DOI
6 Kang H, Remington JS, Suzuki Y. Decreased resistance of B celldeficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-$\gamma$, TNF-${\alpha}$, and inducible nitric oxide synthase. J Immunol 2000; 164: 2629-2634.   DOI
7 Liu KY, Zhang DB, Wei QK, Li J, Li GP, Yu JZ. Biological role of surface Toxoplasma gondii antigen in development of vaccine. World J Gastroenterol 2006; 12: 2363-2368.   DOI
8 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.   DOI
9 Gazzinelli RT, Hieny S, Wynn TA, Wolf S, Sher A. Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proc Natl Acad Sci U S A 1993; 90: 6115-6119.   DOI
10 Machado AV, Caetano BC, Barbosa RP, Salgado AP, Rabelo RH, Garcia CC, Bruna-Romero O, Escriou N, Gazzinelli RT. Prime and boost immunization with influenza and adenovirus encoding the Toxoplasma gondii surface antigen 2 (SAG2) induces strong protective immunity. Vaccine 2010; 28: 3247-3256.   DOI
11 Gazzinelli RT, Wysocka M, Hieny S, Scharton-Kersten T, Cheever A, Kuhn R, Muller 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-$\gamma$. J Immunol 1996; 157: 798-805.
12 Dawson HD, Beshah E, Nishi S, Solano-Aguilar G, Morimoto M, Zhao A, Madden KB, Ledbetter TK, Dubey JP, Shea-Donohue T, Lunney JK, Urban JF Jr. Localized multigene expression patterns support an evolving Th1/Th2-like paradigm in response to infections with Toxoplasma gondii and Ascaris suum. Infect Immun 2005; 73: 1116-1128.   DOI
13 Desolme B, Mevelec MN, Buzoni-Gatel D, Bout D. Induction of protective immunity against toxoplasmosis in mice by DNA immunization with a plasmid encoding Toxoplasma gondii GRA4 gene. Vaccine 2000; 18: 2512-2521.   DOI
14 Zhao G, Zhou A, Lu G, Meng M, Sun M, Bai Y, Han Y, Wang L, Zhou H, Cong H, Zhao Q, Zhu XQ, He S. Identification and characterization of Toxoplasma gondii aspartic protease 1 as a novel vaccine candidate against toxoplasmosis. Parasit Vectors 2013; 6: 175.   DOI
15 Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, Sato M, Takeda K, Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nishimura T. The natural killer T (NKT) cell ligand ${\alpha}$-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 1999; 189: 1121-1128.   DOI
16 Weiss LM, Dubey JP. Toxoplasmosis: a history of clinical observations. Int J Parasitol 2009; 39: 895-901.   DOI
17 Dubey JP. The history of Toxoplasma gondii--the first 100 years. J Eukaryot Microbiol 2008; 55: 467-475.   DOI
18 Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004; 363: 1965-1976.   DOI
19 Cenci-Goga BT, Rossitto PV, Sechi P, McCrindle CM, Cullor JS. Toxoplasma in animals, food, and humans: an old parasite of new concern. Foodborne Pathog Dis 2011; 8: 751-762.   DOI
20 McLeod R, Kieffer F, Sautter M, Hosten T, Pelloux H. Why prevent, diagnose and treat congenital toxoplasmosis? Mem Inst Oswaldo Cruz 2009; 104: 320-344.   DOI
21 Andrade GM, Vasconcelos-Santos DV, Carellos EV, Romanelli RM, Vitor RW, Carneiro AC, Januario JN. Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy. J Pediatr (Rio J) 2010; 86: 85-88.   DOI
22 Kakimi K, Guidotti LG, Koezuka Y, Chisari FV. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 2000; 192: 921-930.   DOI
23 Ichikawa T, Negishi Y, Shimizu M, Takeshita T, Takahashi H. ${\alpha}$-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice. Eur J Immunol 2016; 46: 1867-1877.   DOI
24 Meng M, Zhou A, Lu G, Wang L, Zhao G, Han Y, Zhou H, Cong H, Zhao Q, Zhu XQ, He S. DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice. BMC Infect Dis 2013; 13: 494.   DOI
25 Jongert E, Roberts CW, Gargano N, Forster-Waldl E, Petersen E. Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz 2009; 104: 252-266.
26 Hiszczynska-Sawicka E, Holec-Gasior L, Kur J. DNA vaccines and recombinant antigens in prevention of Toxoplasma gondii infections-current status of the studies. Wiad Parazytol 2009; 55: 125-139.
27 Que X, Engel JC, Ferguson D, Wunderlich A, Tomavo S, Reed SL. Cathepsin Cs are key for the intracellular survival of the protozoan parasite, Toxoplasma gondii. J Biol Chem 2007; 282: 4994-5003.   DOI
28 Dou Z, Carruthers VB. Cathepsin proteases in Toxoplasma gondii. Adv Exp Med Biol 2011; 712: 49-61.
29 Saade F, Petrovsky N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines 2012; 11: 189-209.   DOI
30 Kamijuku H, Nagata Y, Jiang X, Ichinohe T, Tashiro T, Mori K, Taniguchi M, Hase K, Ohno H, Shimaoka T, Yonehara S, Odagiri T, Tashiro M, Sata T, Hasegawa H, Seino KI. Mechanism of NKT cell activation by intranasal coadministration of ${\alpha}$-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol 2008; 1: 208-218.   DOI
31 Dhodapkar MV, Richter J. Harnessing natural killer T (NKT) cells in human myeloma: progress and challenges. Clin Immunol 2011; 140: 160-166.   DOI
32 Cong H, Gu QM, Yin HE, Wang JW, Zhao QL, Zhou HY, Li Y, Zhang JQ. Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii. Vaccine 2008; 26: 3913-3921.   DOI
33 Gonzalez-Aseguinolaza G, Van Kaer L, Bergmann CC, Wilson JM, Schmieg J, Kronenberg M, Nakayama T, Taniguchi M, Koezuka Y, Tsuji M. Natural killer T cell ligand ${\alpha}$-galactosylceramide enhances protective immunity induced by malaria vaccines. J Exp Med 2002; 195: 617-624.   DOI
34 Lu G, Zhou A, Meng M, Wang L, Han Y, Guo J, Zhou H, Cong H, Zhao Q, Zhu XQ, He S. ${\alpha}$-Galactosylceramide enhances protective immunity induced by DNA vaccine of the SAG5D gene of Toxoplasma gondii. BMC Infect Dis 2014; 14: 3862.   DOI
35 Bai Y, He S, Zhao G, Chen L, Shi N, Zhou H, Cong H, Zhao Q, Zhu XQ. Toxoplasma gondii: bioinformatics analysis, cloning and expression of a novel protein TgIMP1. Exp Parasitol 2012; 132: 458-464.   DOI
36 Van Regenmortel MH. What is a B-cell epitope? Methods Mol Biol 2009; 524: 3-20.
37 Gao J, Faraggi E, Zhou Y, Ruan J, Kurgan L. BEST: improved prediction of B-cell epitopes from antigen sequences. PLoS One 2012; 7: e40104.   DOI
38 Romano P, Giugno R, Pulvirenti A. Tools and collaborative environments for bioinformatics research. Brief Bioinform 2011; 12: 549-561.   DOI
39 Reilly EC, Thompson EA, Aspeslagh S, Wands JR, Elewaut D, Brossay L. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection. PLoS One 2012; 7: e37991.   DOI
40 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.   DOI
41 Martin DM, Berriman M, Barton GJ. GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes. BMC Bioinformatics 2004; 5: 178.   DOI