Skip to main content
Top
Published in: BMC Infectious Diseases 1/2013

Open Access 01-12-2013 | Research article

Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis

Authors: Guanghui Zhao, Aihua Zhou, Gang Lv, Min Meng, Min Sun, Yang Bai, Yali Han, Lin Wang, Huaiyu Zhou, Hua Cong, Qunli Zhao, Xing-Quan Zhu, Shenyi He

Published in: BMC Infectious Diseases | Issue 1/2013

Login to get access

Abstract

Background

Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii.

Methods

Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines.

Results

TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection.

Conclusions

T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dubey JP, Su C: Population biology of Toxoplasma gondii: what’s out and where did they come from. Memórias do Instituto Oswaldo Cruz. 2009, 104 (2): 190-195. 10.1590/S0074-02762009000200011.CrossRefPubMed Dubey JP, Su C: Population biology of Toxoplasma gondii: what’s out and where did they come from. Memórias do Instituto Oswaldo Cruz. 2009, 104 (2): 190-195. 10.1590/S0074-02762009000200011.CrossRefPubMed
2.
go back to reference Dubey JP: The history of Toxoplasma gondii–the first 100 years. J Eukaryot Microbiol. 2008, 55 (6): 467-475. 10.1111/j.1550-7408.2008.00345.x.CrossRefPubMed Dubey JP: The history of Toxoplasma gondii–the first 100 years. J Eukaryot Microbiol. 2008, 55 (6): 467-475. 10.1111/j.1550-7408.2008.00345.x.CrossRefPubMed
3.
go back to reference Montoya JG, Liesenfeld O: Toxoplasmosis. Lancet. 2004, 363 (9425): 1965-1976. 10.1016/S0140-6736(04)16412-X.CrossRefPubMed Montoya JG, Liesenfeld O: Toxoplasmosis. Lancet. 2004, 363 (9425): 1965-1976. 10.1016/S0140-6736(04)16412-X.CrossRefPubMed
4.
go back to reference Robert-Gangneux F, Darde ML: Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012, 25 (2): 264-296. 10.1128/CMR.05013-11.CrossRefPubMedPubMedCentral Robert-Gangneux F, Darde ML: Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012, 25 (2): 264-296. 10.1128/CMR.05013-11.CrossRefPubMedPubMedCentral
5.
go back to reference Luft BJ, Hafner R, Korzun AH, Leport C, Antoniskis D: Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1993, 329 (14): 995-1000. 10.1056/NEJM199309303291403.CrossRefPubMed Luft BJ, Hafner R, Korzun AH, Leport C, Antoniskis D: Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1993, 329 (14): 995-1000. 10.1056/NEJM199309303291403.CrossRefPubMed
6.
go back to reference Afonso C, Paixão VB, Costa RM: Chronic Toxoplasma infection modifies the structure and the risk of host behavior. PLoS One. 2012, 7 (3): e32489 p-CrossRef Afonso C, Paixão VB, Costa RM: Chronic Toxoplasma infection modifies the structure and the risk of host behavior. PLoS One. 2012, 7 (3): e32489 p-CrossRef
7.
go back to reference Dass SA, Vasudevan A, Dutta D, Soh LJ, Sapolsky RM: Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males. PLoS One. 2011, 6 (11): e27229 p-CrossRef Dass SA, Vasudevan A, Dutta D, Soh LJ, Sapolsky RM: Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males. PLoS One. 2011, 6 (11): e27229 p-CrossRef
8.
go back to reference Haroon F, Händel U, Angenstein F, Goldschmidt J, Kreutzmann P: Toxoplasma gondii actively inhibits neuronal function in chronically infected mice. PLoS One. 2012, 7 (4): e35516 p-CrossRef Haroon F, Händel U, Angenstein F, Goldschmidt J, Kreutzmann P: Toxoplasma gondii actively inhibits neuronal function in chronically infected mice. PLoS One. 2012, 7 (4): e35516 p-CrossRef
9.
go back to reference Bhopale GM: Development of a vaccine for toxoplasmosis: current status. Microbes and Infection. 2003, 5 (5): 457-462. 10.1016/S1286-4579(03)00048-0.CrossRefPubMed Bhopale GM: Development of a vaccine for toxoplasmosis: current status. Microbes and Infection. 2003, 5 (5): 457-462. 10.1016/S1286-4579(03)00048-0.CrossRefPubMed
10.
go back to reference Hiszczynska-Sawicka E, Holec-Gasior L, Kur J: DNA vaccines and recombinant antigens in prevention of Toxoplasma gondii infections—current status of the studies. Wiadomości Parazytologiczne. 2009, 55 (2): 125-139.PubMed Hiszczynska-Sawicka E, Holec-Gasior L, Kur J: DNA vaccines and recombinant antigens in prevention of Toxoplasma gondii infections—current status of the studies. Wiadomości Parazytologiczne. 2009, 55 (2): 125-139.PubMed
11.
go back to reference Liu Q, Singla LD, Zhou H: Vaccines against Toxoplasma gondii: status, challen ges and future directions. Hum Vaccin Immunother. 2012, 8 (9): 1305-1308. 10.4161/hv.21006.CrossRefPubMedPubMedCentral Liu Q, Singla LD, Zhou H: Vaccines against Toxoplasma gondii: status, challen ges and future directions. Hum Vaccin Immunother. 2012, 8 (9): 1305-1308. 10.4161/hv.21006.CrossRefPubMedPubMedCentral
12.
go back to reference Barrett AJ, Kirschke H: Cathepsin B, Cathepsin H, and Cathepsin L. Methods Enzymol. 1981, 80: 535-561.CrossRefPubMed Barrett AJ, Kirschke H: Cathepsin B, Cathepsin H, and Cathepsin L. Methods Enzymol. 1981, 80: 535-561.CrossRefPubMed
13.
go back to reference Amuthan G, Biswas G, Zhang SY, Klein-Szanto A, Vijayasarathy C: Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. EMBO J. 2001, 20 (8): 1910-1920. 10.1093/emboj/20.8.1910.CrossRefPubMedPubMedCentral Amuthan G, Biswas G, Zhang SY, Klein-Szanto A, Vijayasarathy C: Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. EMBO J. 2001, 20 (8): 1910-1920. 10.1093/emboj/20.8.1910.CrossRefPubMedPubMedCentral
14.
go back to reference Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA: Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Investig. 2000, 106 (9): 1127-1137. 10.1172/JCI9914.CrossRefPubMedPubMedCentral Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA: Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Investig. 2000, 106 (9): 1127-1137. 10.1172/JCI9914.CrossRefPubMedPubMedCentral
15.
go back to reference Dou Z, Carruthers VB: Cathepsin proteases in Toxoplasma gondii. Advances in Experimental Medicine and Biology. 2011, 712: 49-61. 10.1007/978-1-4419-8414-2_4.CrossRefPubMedPubMedCentral Dou Z, Carruthers VB: Cathepsin proteases in Toxoplasma gondii. Advances in Experimental Medicine and Biology. 2011, 712: 49-61. 10.1007/978-1-4419-8414-2_4.CrossRefPubMedPubMedCentral
16.
go back to reference Que X, Ngo H, Lawton J, Gray M, Liu Q: The cathepsin B of Toxoplasma gondii, toxopain-1, is critical for parasite invasion and rhoptry protein processing. J Biol Chem. 2002, 277 (28): 25791-25797. 10.1074/jbc.M202659200.CrossRefPubMed Que X, Ngo H, Lawton J, Gray M, Liu Q: The cathepsin B of Toxoplasma gondii, toxopain-1, is critical for parasite invasion and rhoptry protein processing. J Biol Chem. 2002, 277 (28): 25791-25797. 10.1074/jbc.M202659200.CrossRefPubMed
17.
go back to reference Parussini F, Coppens I, Shah PP, Diamond SL, Carruthers VB: Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondii. Mol Microbiol. 2010, 76 (6): 1340-1357. 10.1111/j.1365-2958.2010.07181.x.CrossRefPubMedPubMedCentral Parussini F, Coppens I, Shah PP, Diamond SL, Carruthers VB: Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondii. Mol Microbiol. 2010, 76 (6): 1340-1357. 10.1111/j.1365-2958.2010.07181.x.CrossRefPubMedPubMedCentral
18.
go back to reference Miranda K, Pace DA, Cintron R, Rodrigues JC, Fang J: Characterization of a novel organelle in Toxoplasma gondii with similar composition and function to the plant vacuole. Mol Microbiol. 2010, 76 (6): 1358-1375. 10.1111/j.1365-2958.2010.07165.x.CrossRefPubMedPubMedCentral Miranda K, Pace DA, Cintron R, Rodrigues JC, Fang J: Characterization of a novel organelle in Toxoplasma gondii with similar composition and function to the plant vacuole. Mol Microbiol. 2010, 76 (6): 1358-1375. 10.1111/j.1365-2958.2010.07165.x.CrossRefPubMedPubMedCentral
19.
go back to reference Huang R, Que X, Hirata K, Brinen LS, Lee JH: The cathepsin L of Toxoplasma gondii (TgCPL) and its endogenous macromolecular inhibitor, toxostatin. Mol Biochem Parasitol. 2009, 164 (1): 86-94. 10.1016/j.molbiopara.2008.11.012.CrossRefPubMed Huang R, Que X, Hirata K, Brinen LS, Lee JH: The cathepsin L of Toxoplasma gondii (TgCPL) and its endogenous macromolecular inhibitor, toxostatin. Mol Biochem Parasitol. 2009, 164 (1): 86-94. 10.1016/j.molbiopara.2008.11.012.CrossRefPubMed
20.
go back to reference Harper JM, Huynh MH, Coppens I, Parussini F, Moreno S: A cleavable propeptide influences Toxoplasma infection by facilitating the trafficking and secretion of the TgMIC2-M2AP invasion complex. Molecular Biology of the Cell. 2006, 17 (10): 4551-4563. 10.1091/mbc.E06-01-0064.CrossRefPubMedPubMedCentral Harper JM, Huynh MH, Coppens I, Parussini F, Moreno S: A cleavable propeptide influences Toxoplasma infection by facilitating the trafficking and secretion of the TgMIC2-M2AP invasion complex. Molecular Biology of the Cell. 2006, 17 (10): 4551-4563. 10.1091/mbc.E06-01-0064.CrossRefPubMedPubMedCentral
21.
go back to reference El Hajj H, Papoin J, Cérède O, Garcia-Réguet N, Soête M: Molecular signals in the trafficking of Toxoplasma gondii protein MIC3 to the micronemes. Eukaryotic Cell. 2008, 7 (6): 1019-1028. 10.1128/EC.00413-07.CrossRefPubMedPubMedCentral El Hajj H, Papoin J, Cérède O, Garcia-Réguet N, Soête M: Molecular signals in the trafficking of Toxoplasma gondii protein MIC3 to the micronemes. Eukaryotic Cell. 2008, 7 (6): 1019-1028. 10.1128/EC.00413-07.CrossRefPubMedPubMedCentral
22.
go back to reference Rabenau KE, Sohrabi A, Tripathy A, Reitter C, Ajioka JW: TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2. Mol Microbiol. 2001, 41 (3): 537-547. 10.1046/j.1365-2958.2001.02513.x.CrossRefPubMed Rabenau KE, Sohrabi A, Tripathy A, Reitter C, Ajioka JW: TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2. Mol Microbiol. 2001, 41 (3): 537-547. 10.1046/j.1365-2958.2001.02513.x.CrossRefPubMed
23.
go back to reference Brydges SD, Sherman GD, Nockemann S, Loyens A, Däubener W: Molecular characterization of TgMIC5, a proteolytically processed antigen secreted from the micronemes of Toxoplasma gondii. Mol Biochem Parasitol. 2000, 111 (1): 51-66. 10.1016/S0166-6851(00)00296-6.CrossRefPubMed Brydges SD, Sherman GD, Nockemann S, Loyens A, Däubener W: Molecular characterization of TgMIC5, a proteolytically processed antigen secreted from the micronemes of Toxoplasma gondii. Mol Biochem Parasitol. 2000, 111 (1): 51-66. 10.1016/S0166-6851(00)00296-6.CrossRefPubMed
24.
go back to reference Que X, Wunderlich A, Joiner KA, Reed SL: Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis. Infect Immun. 2004, 72 (5): 2915-2921. 10.1128/IAI.72.5.2915-2921.2004.CrossRefPubMedPubMedCentral Que X, Wunderlich A, Joiner KA, Reed SL: Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis. Infect Immun. 2004, 72 (5): 2915-2921. 10.1128/IAI.72.5.2915-2921.2004.CrossRefPubMedPubMedCentral
25.
go back to reference Teo CF, Zhou XW, Bogyo M, Carruthers VB: Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion. Antimicrob Agents Chemother. 2007, 51 (2): 679-688. 10.1128/AAC.01059-06.CrossRefPubMed Teo CF, Zhou XW, Bogyo M, Carruthers VB: Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion. Antimicrob Agents Chemother. 2007, 51 (2): 679-688. 10.1128/AAC.01059-06.CrossRefPubMed
26.
go back to reference Larson ET, Parussini F, Huynh MH, Giebel JD, Kelley AM: Toxoplasma gondii cathepsin l is the primary target of the invasion inhibitory compound LHVS. J Biol Chem. 2009, 284 (39): 26839-26850. 10.1074/jbc.M109.003780.CrossRefPubMedPubMedCentral Larson ET, Parussini F, Huynh MH, Giebel JD, Kelley AM: Toxoplasma gondii cathepsin l is the primary target of the invasion inhibitory compound LHVS. J Biol Chem. 2009, 284 (39): 26839-26850. 10.1074/jbc.M109.003780.CrossRefPubMedPubMedCentral
27.
go back to reference Gao J, Faraggi E, Zhou Y, Ruan J, Kurgan L: BEST: improved prediction of B-cell epitopes from antigen sequences. PLoS One. 2012, 7 (6): e40104 p-CrossRef Gao J, Faraggi E, Zhou Y, Ruan J, Kurgan L: BEST: improved prediction of B-cell epitopes from antigen sequences. PLoS One. 2012, 7 (6): e40104 p-CrossRef
28.
go back to reference Van Regenmortel MH: What is a B-cell epitope?. Methods in Molecular Biology. 2009, 524: 3-20. 10.1007/978-1-59745-450-6_1.CrossRefPubMed Van Regenmortel MH: What is a B-cell epitope?. Methods in Molecular Biology. 2009, 524: 3-20. 10.1007/978-1-59745-450-6_1.CrossRefPubMed
29.
go back to reference Tong JC, Tammi MT: Prediction of protein allergenicity using local description of amino acid sequence. Front Biosci. 2008, 13: 6072-6078.CrossRefPubMed Tong JC, Tammi MT: Prediction of protein allergenicity using local description of amino acid sequence. Front Biosci. 2008, 13: 6072-6078.CrossRefPubMed
30.
go back to reference Carter JM, Loomis-Price L: B cell epitope mapping using synthetic peptides. Current Protoc Immunol. 2004, 10.1002/0471142735.im0904s60. Chapter 9:Unit 9.4 Carter JM, Loomis-Price L: B cell epitope mapping using synthetic peptides. Current Protoc Immunol. 2004, 10.1002/0471142735.im0904s60. Chapter 9:Unit 9.4
31.
go back to reference Kyte J, Doolittle RF: A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982, 157 (1): 105-132. 10.1016/0022-2836(82)90515-0.CrossRefPubMed Kyte J, Doolittle RF: A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982, 157 (1): 105-132. 10.1016/0022-2836(82)90515-0.CrossRefPubMed
32.
go back to reference Welling GW, Weijer WJ, van der Zee R, Welling-Wester S: Prediction of sequential antigenic regions in proteins. FEBS Lett. 1985, 188 (2): 215-218. 10.1016/0014-5793(85)80374-4.CrossRefPubMed Welling GW, Weijer WJ, van der Zee R, Welling-Wester S: Prediction of sequential antigenic regions in proteins. FEBS Lett. 1985, 188 (2): 215-218. 10.1016/0014-5793(85)80374-4.CrossRefPubMed
33.
go back to reference Subramani A, Floudas CA: Structure prediction of loops with fixed and flexible stems. The Journal of Physical Chemistry. B. 2012, 116 (23): 6670-6682. 10.1021/jp2113957.CrossRefPubMedPubMedCentral Subramani A, Floudas CA: Structure prediction of loops with fixed and flexible stems. The Journal of Physical Chemistry. B. 2012, 116 (23): 6670-6682. 10.1021/jp2113957.CrossRefPubMedPubMedCentral
34.
go back to reference Gershoni JM, Stern B, Denisova G: Combinatorial libraries, epitope structure and the prediction of protein conformations. Immunol Today. 1997, 18 (3): 108-110. 10.1016/S0167-5699(97)01024-4.CrossRefPubMed Gershoni JM, Stern B, Denisova G: Combinatorial libraries, epitope structure and the prediction of protein conformations. Immunol Today. 1997, 18 (3): 108-110. 10.1016/S0167-5699(97)01024-4.CrossRefPubMed
35.
go back to reference El-Kady IM: T-cell immunity in human chronic toxoplasmosis. J Egypt Soc Parasitol. 2011, 41 (1): 17-28.PubMed El-Kady IM: T-cell immunity in human chronic toxoplasmosis. J Egypt Soc Parasitol. 2011, 41 (1): 17-28.PubMed
36.
go back to reference Bhasin M, Lata S, Raghava GP: Searching and mapping of T-cell epitopes, MHC binders, and TAP binders. Methods in Molecular Biology. 2007, 409: 95-112. 10.1007/978-1-60327-118-9_6.CrossRefPubMed Bhasin M, Lata S, Raghava GP: Searching and mapping of T-cell epitopes, MHC binders, and TAP binders. Methods in Molecular Biology. 2007, 409: 95-112. 10.1007/978-1-60327-118-9_6.CrossRefPubMed
37.
go back to reference Vider-Shalit T, Louzoun Y: MHC-I prediction using a combination of T cell epitopes and MHC-I binding peptides. J Immunol Methods. 2011, 374 (1–2): 43-46.CrossRefPubMed Vider-Shalit T, Louzoun Y: MHC-I prediction using a combination of T cell epitopes and MHC-I binding peptides. J Immunol Methods. 2011, 374 (1–2): 43-46.CrossRefPubMed
38.
go back to reference Zhou H, Min J, Zhao Q, Gu Q, Cong H: Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant. Vaccine. 2012, 30 (10): 1800-1806. 10.1016/j.vaccine.2012.01.004.CrossRefPubMed Zhou H, Min J, Zhao Q, Gu Q, Cong H: Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant. Vaccine. 2012, 30 (10): 1800-1806. 10.1016/j.vaccine.2012.01.004.CrossRefPubMed
39.
go back to reference Cui X, Lei T, Yang D, Hao P, Li B, Liu Q: Toxoplasma gondii immune mapped protein-1 (TgIMP1) is a novel vaccine candidate against toxoplasmosis. Vaccine. 2012, 30 (13): 2282-2287. 10.1016/j.vaccine.2012.01.073.CrossRefPubMed Cui X, Lei T, Yang D, Hao P, Li B, Liu Q: Toxoplasma gondii immune mapped protein-1 (TgIMP1) is a novel vaccine candidate against toxoplasmosis. Vaccine. 2012, 30 (13): 2282-2287. 10.1016/j.vaccine.2012.01.073.CrossRefPubMed
40.
go back to reference Min J, Qu D, Li C, Song X, Zhao Q: Enhancement of protective immune responses induced by Toxoplasma gondii dense granule antigen 7 (GRA7) against toxoplasmosis in mice using a prime-boost vaccination strategy. Vaccine. 2012, 30 (38): 5631-5636. 10.1016/j.vaccine.2012.06.081.CrossRefPubMed Min J, Qu D, Li C, Song X, Zhao Q: Enhancement of protective immune responses induced by Toxoplasma gondii dense granule antigen 7 (GRA7) against toxoplasmosis in mice using a prime-boost vaccination strategy. Vaccine. 2012, 30 (38): 5631-5636. 10.1016/j.vaccine.2012.06.081.CrossRefPubMed
41.
go back to reference Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K: Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. The Journal of Experimental Medicine. 1995, 182 (5): 1591-1596. 10.1084/jem.182.5.1591.CrossRefPubMed Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K: Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. The Journal of Experimental Medicine. 1995, 182 (5): 1591-1596. 10.1084/jem.182.5.1591.CrossRefPubMed
42.
go back to reference Chaturvedi P, Yu Q, Southwood S, Sette A, Singh B: Peptide analogs with different affinites for MHC alter the cytokine profile of T helper cells. Int Immunol. 1996, 8 (5): 745-755. 10.1093/intimm/8.5.745.CrossRefPubMed Chaturvedi P, Yu Q, Southwood S, Sette A, Singh B: Peptide analogs with different affinites for MHC alter the cytokine profile of T helper cells. Int Immunol. 1996, 8 (5): 745-755. 10.1093/intimm/8.5.745.CrossRefPubMed
43.
go back to reference Romano P, Giugno R, Pulvirenti A: Tools and collaborative environments for bioinformatics research. Briefings in Bioinformatics. 2011, 12 (6): 549-561. 10.1093/bib/bbr055.CrossRefPubMedPubMedCentral Romano P, Giugno R, Pulvirenti A: Tools and collaborative environments for bioinformatics research. Briefings in Bioinformatics. 2011, 12 (6): 549-561. 10.1093/bib/bbr055.CrossRefPubMedPubMedCentral
44.
go back to reference Martin DM, Berriman M, Barton GJ: GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes. BMC Bioinforma. 2004, 5: 178-10.1186/1471-2105-5-178.CrossRef Martin DM, Berriman M, Barton GJ: GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes. BMC Bioinforma. 2004, 5: 178-10.1186/1471-2105-5-178.CrossRef
45.
go back to reference 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 (4): 458-464. 10.1016/j.exppara.2012.09.015.CrossRefPubMed 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 (4): 458-464. 10.1016/j.exppara.2012.09.015.CrossRefPubMed
46.
go back to reference Mannie MD: Do holes in the T-cell repertoire have a center-surround regulatory structure? A rationale for the bifurcation of the Th1 and Th2 pathways of differentiation. Medical Hypotheses. 1997, 8 (3): 261-265.CrossRef Mannie MD: Do holes in the T-cell repertoire have a center-surround regulatory structure? A rationale for the bifurcation of the Th1 and Th2 pathways of differentiation. Medical Hypotheses. 1997, 8 (3): 261-265.CrossRef
47.
go back to reference Schaeffer EB, Sette A, Johnson DL, Bekoff MC, Smith JA, Grey HM, Buus S: Relative contribution of “determinant selection” and “holes in the T-cell repertoire” to T-cell responses. Proc Natl Acad Sci USA. 1989, 86 (12): 4649-4653. 10.1073/pnas.86.12.4649.CrossRefPubMedPubMedCentral Schaeffer EB, Sette A, Johnson DL, Bekoff MC, Smith JA, Grey HM, Buus S: Relative contribution of “determinant selection” and “holes in the T-cell repertoire” to T-cell responses. Proc Natl Acad Sci USA. 1989, 86 (12): 4649-4653. 10.1073/pnas.86.12.4649.CrossRefPubMedPubMedCentral
Metadata
Title
Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis
Authors
Guanghui Zhao
Aihua Zhou
Gang Lv
Min Meng
Min Sun
Yang Bai
Yali Han
Lin Wang
Huaiyu Zhou
Hua Cong
Qunli Zhao
Xing-Quan Zhu
Shenyi He
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2013
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-13-207

Other articles of this Issue 1/2013

BMC Infectious Diseases 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.