日本血吸虫多表位疫苗构建探索和TSP-2抗原鉴定
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摘要
血吸虫病是世界上严重危害人类健康的寄生虫病之一,流行于世界上76个国家和地区,目前有2亿感染者。流行于我国的日本血吸虫病是所有血吸虫病中防治难度最大的一种。利用吡喹酮治疗在控制该病的过程中起到重要作用,但治疗后的反复感染,及反复化疗可能产生抗药性问题,使得仅靠单一药物治疗无法从根本上控制血吸虫病的传播。研发安全有效的抗血吸虫疫苗,单独使用或结合化疗将极大地推动血吸虫病的防治工作。但早期研制的疫苗,从安全性或保护效果来看并不令人满意。因此,新型抗原的鉴定和新型疫苗的研制是一项十分紧迫的任务。
     本研究通过生物信息学方法,从日本血吸虫的8个关键抗原中筛查18个表位,其中5个在日本血吸虫中鉴定,其余13个为曼氏血吸虫中鉴定的表位在日本血吸虫中的同源序列。利用表位改组技术成功构建5个不同长度的随机串联多表位人工抗原文库,并证明文库具有良好的表位串联多态性。
     不同文库免疫小鼠后抗体水平的检测,表明多表位基因的长度对文库的抗原性具有显著的影响。保护性实验结果显示5个文库的保护效果并不理想,可能与所选的多数表位并未在日本血吸虫中得到有效证实有关。文库L2取得部分的抗生殖作用,表明只有合适长度的多表位基因文库才有可能诱导较好的免疫保护作用。
     通过上述工作,证实新型表位改组技术能应用于不同病原体多表位文库的构建,确定可能诱导保护性免疫反应的多表位基因长度;同时提示要构建具有高保护性的日本血吸虫多表位人工抗原文库,仍有待于保护性表位的鉴定。
     曼氏血吸虫表膜四次跨膜蛋白家族成员被认为是具有保护潜力的抗原分子,其中是曼氏血吸虫新型抗原TSP-2更是获得高达~60%的保护力,本研究对Sm-TSP-2在日本血吸虫中的同源分子展开鉴定和评估。研究证实日本血吸虫Sj-TSP-2分子存在广泛变异,根据C、D变异区不同,可分为七个亚类,同时存在不同亚类之间重组的杂合分子;三级结果预测显示主要变异区暴露于分子的表面,表明此分子受正选择作用,并提示其配体的多样性;单一成虫RT-PCR显示Sj-tsp-2亚类表达谱在个体成虫中存在极大的差异,以上研究结果提示Sj-stp-2可能参与日本血吸虫的免疫逃避。
     半定量RT-PCR表明Sj-tsp-2基因在日本血吸虫尾蚴、童虫、雌雄成虫和虫卵中都有不同水平的转录;但Western blot分析显示Sj-TSP-2蛋白并不在虫卵期表达。免疫荧光定位实验表明Sj-TSP-2定位于肺期童虫的表膜,但在天然状态下并不暴露;而活体成虫及冰冻切片免疫荧光实验则证实Sj-TSP-2分子暴露于雌雄成虫的体表。
     免疫保护实验显示单一Sj-TSP-2亚类重组蛋白不能获得任何的保护效果,所有亚类重组蛋白的混合物也只获得较低的保护力,再次提示Sj-TSP-2分子与免疫逃避相关,变异如此广泛的Sj-TSP-2并不适合成为日本血吸虫的候选抗原。
     以上工作显示表膜蛋白TSP-2在曼氏血吸虫和日本血吸虫中极大的差异性,说明曼氏血吸虫的保护性抗原,其在日本血吸虫中的同源分子并不一定同样具有保护性;提示在不同环境压力下,日本血吸虫可能采取了不同于曼氏血吸虫的免疫逃避策略,在一定程度上佐证了前一部分的结果,进一步强调日本血吸虫特异的保护性抗原和表位的鉴定对于日本血吸虫疫苗的研制的重要性。
Schistosomiasis is one of the most serious parasitic diseases that infect approximately 200 million people living in the endemic areas of 76 countries and territories. Schistosomiasis japonica which is the one most hard to be prevented is still endemic in China today. Chemotherapy, using praziquantel (PZQ) play an important role in controlling the disease, but repeated infection and potential drug resistance render all chemotherapy-based control strategies inadequate. Therefore, safe and effective vaccine, alone or in combination with anthelmintic drugs would provide a major boost in the disease control program. However, a handful of antigens tested so far are not satisfied because of safety or efficacy which makes the identification of protective antigens and development of novel vaccines an urgent task.
     Using methods of bioinformatics, 18 B and/or T epitopes were selected from 8 key antigens of Schistosoma japonicum. Among them, 5 were identified in S. japonicum and another 13 were the homologous sequence of protective epitopes identified in Schistosoma mansoni. Five libraries with different polyepitope gene length were successfully constructed by the epitope shuffling technique. Each polyepitope library was shown the higher diversity of polyepitope genes based on the PCR analysis.
     With the polyepitope library immunization in mice, we have proved that the length of polyepitope gene affects the antigenicity of DNA library. Protective efficacy elicited by the five libraries were not so satisfied, probably because of the most epitopes selected were not truly identified in S. japonicum. Library L2 induced a moderate anti-fecundity effect in mouse model suggesting that only the library with appropriate polyepitope gene length can elicit protective immunity.
     According to the work above, we proved that the novel epitope shuffling technique can be widely used in constructing polyepitope library against various pathogens and confirmed the gene length of library which may induce protective immune response. Further, in order to construct polyepitope library against S. japonicum with high protection, vigorous endeavor should be made for protective epitope identification.
     Members of tetraspanin family expressed on the tegument of Schistosoma mansoni have been regarded as potential protective antigens, especial the novel tegumental antigen tetraspanin-2 (TSP-2) which induced as high as~60% protection in S. mansoni. So, the identification and evaluation of its homolog in S. japonicum were also carried out. Surprisingly, seven Sj-tsp-2 subclasses were identified according to the sequence variation in C and D variable regions, and hybrid Sj-tsp-2 cDNAs among different subclasses were also detected. 3D prediction revealed that the variable region was exposed on the surface of Sj-TSP-2 protein, suggesting this molecule were under positive selection, thus implicated that polymorphism of its potential ligands. Single worm RT-PCR showed that the transcription profiles of Sj-tsp-2 subclasses were highly variable in individual adult worms. All results above prompted that the Sj-tsp-2 was involved in immune evasion of S. japonicum.
     A semi-quantitative RT-PCR analysis revealed that Sj-tsp-2 gene was transcribed in cercariae, schistosomula, adult worms and eggs; however, Western blot analysis indicated that the Sj-TSP-2 protein was not expressed in eggs. In immunofluorescence assays (IFA), Sj-TSP-2 could be detected on the tegument of schistosomula, but not directly exposed to the host. However, IFA on live adult worms and cryosections showed that Sj-TSP-2 was obviously exposed on the surface of both male and female worms.
     Mice immunized with the recombinant protein of a single Sj-TSP-2 subclass showed no protection, while immunized with a mixture of seven recombinant Sj-TSP-2 subclasses provided a moderate protection. Those data implicated that the tegument protein Sj-TSP-2 may be involved in immune evasion and highly polymorphic of this molecule must affect its potential as a vaccine candidate.
     Thus, an impressive divergence of tegumental TSP-2 molecule was shown between the two species of S. mansoni and S. japonicum in above work. These results demonstrated that the homolog in S. japonicum of the protective antigen identified in S. mansoni may obtain no protection at all, thus indicated that living under the different environmental pressure, S. japonicum may adopt immune evasion strategies differed from that of S. mansoni. In some degree, this fact gives a circumstantial evidence to the result of the frontal part, underlining the importance of identification of specific protective antigens and epitopes for the development of S. japonicum vaccine.
引文
1. WHO: TDR Strategic Direction for Research: Schistosomiasis. Ed, World Health Organization, Geneve 2002.
    2. Chitsulo L, Engels D, Montresor A, Savioli L: The global status of schistosomiasis and its control. Acta tropica 2000, 77(1):41-51.
    3. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D: Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta tropica 2003, 86(2-3):125-139.
    4. King CH, Dickman K, Tisch DJ: Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 2005, 365(9470): 1561-1569.
    5. Wu ZD, Lu ZY, Yu XB: Development of a vaccine against Schistosoma japonicum in China: a review. Acta tropica 2005, 96(2-3): 106-116.
    6. Utzinger J, Zhou XN, Chen MG, Bergquist R: Conquering schistosomiasis in China: the long march. Acta tropica 2005, 96(2-3):69-96.
    7. Liang S, Yang C, Zhong B, Qiu D: Re-emerging schistosomiasis in hilly and mountainous areas of Sichuan, China. Bulletin of the World Health Organization 2006, 84(2): 139-144.
    8. Hao Y, Wu XH, Xia G, Zheng H, Guo JG, Wang LY, Zhou XN: [Schistosomiasis situation in the People Republic of China in 2005. Zhongguoji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 2006, 18(5):321-324.
    9. Chen MG: Use of praziquantel for clinical treatment and morbidity control of schistosomiasis japonica in China: a review of 30 years' experience. Acta tropica 2005, 96(2-3): 168-176.
    10. Gonnert R, Andrews P: Praziquantel, a new board-spectrum antischistosomal agent. Zeitschrift fur Parasitenkunde (Berlin, Germany) 1977, 52(2): 129-150.
    11. Stelma FF, Talla I, Sow S, Kongs A, Niang M, Polman K, Deelder AM, Gryseels B: Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni. The American journal of tropical medicine and hygiene 1995, 53(2): 167-170.
    12. Ismail M, Botros S, Metwally A, William S, Farghally A, Tao LF, Day TA, Bennett JL: Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers. The American journal of tropical medicine and hygiene 1999, 60(6):932-935.
    13. Bergquist NR, Leonardo LR, Mitchell GF: Vaccine-linked chemotherapy: can schistosomiasis control benefit from an integrated approach? Trends in parasitology 2005, 21(3): 112-117.
    14. Shi YE, Jiang CF, Han JJ, Li YL, Ruppel A: Schistosoma japonicum: an ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes. Experimental parasitology 1990, 71(1):100-106.
    15. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Feigner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A et ah Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 1993, 259(5102): 1745-1749.
    16. Michel ML, Davis HL, Schleef M, Mancini M, Tiollais P, Whalen RG: DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans. Proc Natl Acad Sci U S A 1995, 92(12):5307-5311.
    17. Zhou S, Liu S, Song G, Xu Y, Sun W: Protective immunity induced by the full-length cDNA encoding paramyosin of Chinese Schistosoma japonicum. Vaccine 2000,18(27):3196-3204.
    18. Li CM, Shi YE: [Vaccination with a plasmid vector carrying the 26kDa glutathione S-transferase and induced protective immunity against Schistosoma japonicum). Chinese Journal of Parasitic Disease Control 1998, 11(3):207-211.
    19. Scott JC, McManus DP: Molecular cloning and enzymatic expression of the 28-kDa glutathione S-transferase of Schistosoma japonicum: evidence for sequence variation but lack of consistent vaccine efficacy in the murine host. Parasitology international 2000, 49(4):289-300.
    20. Shi F, Zhang Y, Ye P, Lin J, Cai Y, Shen W, Bickle QD, Taylor MG: Laboratory and field evaluation of Schistosoma japonicum DNA vaccines in sheep and water buffalo in China. Vaccine 2001, 20(3-4):462-467.
    21. Zhu Y, Si J, Ham DA, Yu C, He W, Hua W, Yin X, Liang Y, Xu M, Xu R: The protective immunity produced in infected C57BL/6 mice of a DNA vaccine encoding Schistosoma japonicum Chinese strain triose-phosphate isomerase. The Southeast Asian journal of tropical medicine and public health 2002, 33(2):207-213.
    22. Ren JG, Zhu YC, Harn DA, Yu CX, Si J, Yin XR, He W, Xu M, Liang YS, Xu YL et al: [Protective immunity induced with Sjc23 dna vaccine and the enhancing effect of IL-12 as an adjuvant]. Chin J Schislo Control 2001,13(6):328-332.
    23. Zhu YC, Si J, Harn DA, Xu M, Yu CX, Ren JG, Ye P, Yin XR, He W, Xu YL et al: [Protective effects of DNA-plasmid vaccine of Schistosoma japonicum Chinese strain triose-phosphate isomerase in infected pigs]. Chin J Schislo Control 2001,13(5):260-264.
    24. Ren JG, Zhu YC, Harn DA, Yu CX, Si J, Yin XR, He W, Liang YS, Xu M, Hua WQ et al: [Protective immunity effects of co-immunization with sjc23 DNA vaccine and protein vaccine]. ChinJSchislo Control 2002, 14(2):98-101.
    25. Zhu Y, Ren J, Da'dara A, Harn D, Xu M, Si J, Yu C, Liang Y, Ye P, Yin X et al: The protective effect of a Schistosoma japonicum Chinese strain 23 kDa plasmid DNA vaccine in pigs is enhanced with IL-12. Vaccine 2004, 23(1):78-83.
    26. Shi F, Zhang Y, Lin J, Zuo X, Shen W, Cai Y, Ye P, Bickle QD, Taylor MG: Field testing of Schistosoma japonicum DNA vaccines in cattle in China. Vaccine 2002, 20(31-32):3629-3631.
    27. Yu CX, Zhu YC, Yin XR, Ren JG, Si J, Xu YL, Shen LN, He W: [Protective immunity induced by the nucleic acid vaccine of fatty acid bind protein of Schistosoma japonicum Chinese strain (Sjc FABP) in Balb/c mice]. Chin J Schislo Control 2002, 14(3): 163-167.
    28. Zhang YY, Taylor MG, Gregoriadis G, McCrossan MV, Bickle QD: Immunogenicity of plasmid DNA encoding the 62 kDa fragment of Schistosoma japonicum myosin. Vaccine 2000, 18(20):2102-2109.
    29. Bickle QD, Bogh HO, Johansen MV, Zhang Y: Comparison of the vaccine efficacy of gamma-irradiated Schistosoma japonicum cercariae with the defined antigen Sj62(IrV-5) in pigs. Veterinary parasitology 2001,100(1-2):51-62.
    30. Liu Y, Xiao JH, Liao L, Zhang YK, Zeng GQ: [Construction of the nucleic acid vaccine pcDNA3.1(+)/MLP of Schistosoma japonica and its immuno-protective effect on rabbits]. Chinese Journal of Zoonoses 2004, 20(4):299-302.
    31. Zhang R, Yi XY, Zeng XF, Zhang SK, McReynolds L: [Study on protective immunity of cathepsin B DNA vaccine against Schistosoma japonicum]. Acta Parasitologica Et Medica Entomologica Sinica 2004, 11(3):324-327.
    32. Zhou JM, Yu XB, Wu ZD, Zheng YN, Bian GW: [Study on the protective immunity in mice by DAN vaccination with recombinant plasmid encoding Schistosoma japonicum yolk ferritin]. Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 2001,13(6):324-327.
    33. Zhu JG, Lin JJ, Feng XG, Wu XF, Zhou YC, Cai YM: [Preliminary studies on DNA vaccine of cDNA encoding the conservative region of gynecophoral canal protein of Schistosoma japonicum (Chinese strain)). Chinese Journal of Zoonoses 2002, 18(3):27-30.
    34. Gan XX, Shen LY, Wang Y, Ding JZ, Shen HY, Zeng XP, McManus DP, Brindley PJ, Fan J: Recombinant tegumental protein Shistosoma japonicum very lowdensity lipoprotein binding protein as a vaccine candidate against Schistosoma japonicum. Memorias do Instituto Oswaldo Cruz 2006, 101(1):9-13.
    35. Parker SE, Borellini F, Wenk ML, Hobart P, Hoffman SL, Hedstrom R, Le T, Norman JA: Plasmid DNA malaria vaccine: tissue distribution and safety studies in mice and rabbits. Hum Gene Ther 1999,10(5):741-758.
    36. Leitner WW, Ying H, Restifo NP: DNA and RNA-based vaccines: principles, progress and prospects. Vaccine 1999, 18(9-10):765-777.
    37. Xu S, Shi F, Shen W, Lin J, Wang Y, Ye P, Tian E, Qian C, Lin B, Shi Y et al: Vaccination of sheep against Schistosoma japonicum with either glutathione S-transferase, keyhole limpet haemocyanin or the freeze/thaw schistosomula/BCG vaccine. Veterinary parasitology 1995, 58(4):301-312.
    38. Liu S, Song G, Xu Y, Yang W, McManus DP: Immunization of mice with recombinant Sjc26GST induces a pronounced anti-fecundity effect after experimental infection with Chinese Schistosoma japonicum. Vaccine 1995, 13(6):603-607.
    39. Liu SX, Song GC, Xu YX, Yang W, McManus DP: Anti-fecundity immunity induced in pigs vaccinated with recombinant Schistosoma japonicum 26kDa glutathione-S-transferase. Parasite immunology 1995,17(7):355-340.
    40. Shuxian L, Yongkang H, Guangchen S, Xing-song L, Yuxin X, McManus DP: Anti-fecundity immunity to Schistosoma japonicum induced in Chinese water buffaloes (Bos buffelus) after vaccination with recombinant 26 kDa glutathione-S-transferase (reSjc26GST). Veterinary parasitology 1997, 69(1-2):39-47.
    41. Taylor MG, Huggins MC, Shi F, Lin J, Tian E, Ye P, Shen W, Qian CG, Lin BF, Bickle QD: Production and testing of Schistosoma japonicum candidate vaccine antigens in the natural ovine host. Vaccine 1998,16(13):1290-1298.
    42. Wu Z, Liu S, Zhang S, Tong H, Gao Z, Liu Y, Lin D, Liu Z, Wu G, Yi H et al: Persistence of the protective immunity to Schistosoma japonicum in Chinese yellow cattle induced by recombinant 26kDa glutathione-S-transferase (reSjc26GST). Veterinary parasitology 2004, 123(3-4):167-177.
    43. Ramirez BL, Kurtis JD, Wiest PM, Arias P, Aligui F, Acosta L, Peters P, Olds GR: Paramyosin: a candidate vaccine antigen against Schistosoma japonicum. Parasite immunology 1996, 18(1):49-52.
    
    44. McManus DP, Liu S, Song G, Xu Y, Wong JM: The vaccine efficacy of native paramyosin (Sj-97) against Chinese Schistosoma japonicum. International journal for parasitology 1998, 28(11): 1739-1742.
    45. McManus DP: A vaccine against Asian schistosomiasis: the story unfolds. International journal for parasitology 2000, 30(3):265-271.
    46. Cai C, Zhou JC, Zhang SK, Zeng QR, Zeng XF, Yi XY: [Protective immunity against Schistosoma japonicum in mice immunized with recombinant paramyosin]. Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 2001, 13(4): 198-200.
    47. Chen H, Nara T, Zeng X, Satoh M, Wu G, Jiang W, Yi F, Kojima S, Zhang S, Hirayama K: Vaccination of domestic pig with recombinant paramyosin. against Schistosoma japonicum in China. Vaccine 2000, 18(20):2142-2146.
    48. Miao YX, Liu SX: [Vaccination of mice with native triose phosphate isomerase from Schistosoma japonicum]. Chin J Parasitol Parasitic Dis 1996,14(4):257-261.
    49. Zhu Y, Si J, Harn DA, Yu C, Liang Y, Ren J, Yin X, He W, Hua W: The protective immunity of a DNA vaccine encoding Schistosoma japonicum Chinese strain triose-phosphate isomerase in infected BALB/C mice. The Southeast Asian journal of tropical medicine and public health 2004, 35(3):518-522.
    50. Liu JM, Cai XZ, Lin JJ, Fu ZQ, Yang GZ, Shi FH, Cai YM, Shen W, Taylor MG, Wu XF: Gene cloning, expression and vaccine testing of Schistosoma japonicum SjFABP. Parasite immunology 2004, 26(8-9):351-358.
    51. Hanke T, Schneider J, Gilbert SC, Hill AV, McMichael A: DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. Vaccine 1998, 16(4):426-435.
    52. Thomson SA, Burrows SR, Misko IS, Moss DJ, Coupar BE, Khanna R: Targeting a polyepitope protein incorporating multiple class II-restricted viral epitopes to the secretory/endocytic pathway facilitates immune recognition by CD4+ cytotoxic T lymphocytes: a novel approach to vaccine design. J Virol 1998, 72(3):2246-2252.
    53. Velders MP, Weijzen S, Eiben GL, Elmishad AG, Kloetzel PM, Higgins T, Ciccarelli RB, Evans M, Man S, Smith L el al: Defined flanking spacers and enhanced proteolysis is essential for eradication of established tumors by an epitope string DNA vaccine. J Immunol 2001, 166(9):5366-5373.
    54. Yang W, Jackson DC, Zeng Q, McManus DP: Multi-epitope schistosome vaccine candidates tested for protective immunogenicity in mice. Vaccine 2000,19(1): 103-113.
    55. Zhang L, Yang Y, Yang X, Zhao J, Yang J, Liu F, Zhang Z, Wu G, Su C: T cell epitope-based peptide-DNA dual vaccine induces protective immunity against Schistosoma japonicum infection in C57BL/6J mice. Microbes and infection /Institut Pasteur 2008, 10(3):251-259.
    56. Marshall SH: DNA shuffling: induced molecular breeding to produce new generation long-lasting vaccines. Biotechnol Adv 2002, 20(3-4):229-238.
    57. Staudt LM, Brown PO: Genomic views of the immune system*. Annu Rev Immunol 2000, 18:829-859.
    58. Gupta S, Maiden MC: Exploring the evolution of diversity in pathogen populations. Trends Microbiol 2001, 9(4): 181-185.
    59. Suerbaum S: Genetic variability within Helicobacter pylori. Int J Med Microbiol 2000, 290(2): 175-181.
    60. Doolan DL, Hoffman SL: DNA-based vaccines against malaria: status and promise of the Multi-Stage Malaria DNA Vaccine Operation. Int J Parasitol 2001,31(8):753-762.
    61. Chengtao. L, Yanfang. J, Bin. Y, Min. D, Xiaoyun. H, Heng W: construction of malaria multivalent recombinant DNA vaccine with isocaudamer technique. Chinese Journal of Biochemistry and Molecular Biology 1999,15(6):974-977.
    62. Yu Z, Karem KL, Kanangat S, Manickan E, Rouse BT: Protection by minigenes: a novel approach of DNA vaccines. Vaccine 1998,16(17):1660-1667.
    63. Kumar S, Epstein JE, Richie TL, Nkrumah FK, Soisson L, Carucci DJ, Hoffman SL: A multilateral effort to develop DNA vaccines against falciparum malaria. Trends Parasitol 2002, 18(3):129-135.
    64. Hoffman SL, Doolan DL: Can malaria DNA vaccines on their own be as immunogenic and protective as prime-boost approaches to immunization? Dev Biol (Basel) 2000,104:121-132.
    65. Li M, Bi H, Dong W, Xu W, Li Q, Li Y: A recombinant multi-epitope, multi-stage malaria vaccine candidate expressed in Escherichia coli. Chin MedJ (Engl) 1999,112(8):691-697.
    66. Jiang Y, Lin C, Yin B, He X, Mao Y, Dong M, Xu P, Zhang L, Liu B, Wang H: Effects of the configuration of a multi-epitope chimeric malaria DNA vaccine on its antigenicity to mice. Chin Med J (Engl) 1999, 112(8):686-690.
    67. Cai QL, Wei F, Lin YH, Shao DD, Wang H: Immunogenicity of polyepitope libraries assembled by epitope shuffling: an approach to the development of chimeric gene vaccination against malaria. Vaccine 2004, 23(2):267-277.
    68. Cai Q, Peng G, Bu L, Lin Y, Zhang L, Lustigmen S, Wang H: Immunogenicity and in vitro protective efficacy of a polyepitope Plasmodium falciparum candidate vaccine constructed by epitope shuffling. Vaccine 2007, 25(28):5155-5165.
    69. Hockley DJ, McLaren DJ: Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. International journal for parasitology 1973, 3(1): 13-25.
    70. Van Hellemond JJ, Retra K, Brouwers JF, van Balkom BW, Yazdanbakhsh M, Shoemaker CB, Tielens AG: Functions of the tegument of schistosomes: clues from the proteome and lipidome. International journal for parasitology 2006, 36(6):691-699.
    71. Hu W, Yan Q, Shen DK, Liu F, Zhu ZD, Song HD, Xu XR, Wang ZJ, Rong YP, Zeng LC et al: Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource. Nature genetics 2003, 35(2):139-147.
    72. Liu F, Lu J, Hu W, Wang SY, Cui SJ, Chi M, Yan Q, Wang XR, Song HD, Xu XN et al: New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS pathogens 2006, 2(4):e29.
    73. Verjovski-Almeida S, DeMarco R, Martins EA, Guimaraes PE, Ojopi EP, Paquola AC, Piazza JP, Nishiyama MY, Jr., Kitajima JP, Adamson RE et al: Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni. Nature genetics 2003, 35(2): 148-157.
    74. van Balkom BW, van Gestel RA, Brouwers JF, Krijgsveld J, Tielens AG, Heck AJ, van Hellemond JJ: Mass spectrometric analysis of the Schistosoma mansoni tegumental sub-proteome. Journal of proteome research 2005, 4(3):958-966.
    75. Braschi S, Wilson RA: Proteins exposed at the adult schistosome surface revealed by biotinylation. Mol Cell Proteomics 2006, 5(2):347-356.
    76. Braschi S, Curwen RS, Ashton PD, Verjovski-Almeida S, Wilson A: The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction. Proteomics 2006, 6(5): 1471-1482.
    77. Smyth D, McManus DP, Smout MJ, Laha T, Zhang W, Loukas A: Isolation of cDNAs encoding secreted and transmembrane proteins from Schistosoma mansoni by a signal sequence trap method. Infection and immunity 2003, 71(5):2548-2554.
    78. Tran MH, Pearson MS, Bethony JM, Smyth DJ, Jones MK, Duke M, Don TA, McManus DP, Correa-Oliveira R, Loukas A: Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nature medicine 2006, 12(7):835-840.
    79. Fonseca CT, Cunha-Neto E, Goldberg AC, Kalil J, de Jesus AR, Carvalho EM, Correa-Oliveira R, Hammer J, Sidney J, Sette A et ah Identification of paramyosin T cell epitopes associated with human resistance to Schistosoma mansoni reinfection. Clinical and experimental immunology 2005, 142(3):539-547.
    80. Nara T, Tanabe K, Mahakunkijcharoen Y, Osada Y, Matsumoto N, Kita K, Kojima S: The B cell epitope of paramyosin recognized by a protective monoclonal IgE antibody to Schistosoma japonicum. Vaccine 1997, 15(1):79-84.
    81. Fonseca CT, Cunha-Neto E, Kalil J, Jesus AR, Correa-Oliveira R, Carvalho EM, Oliveira SC: Identification of immunodominant epitopes of Schistosoma mansoni vaccine candidate antigens using human T cells. Memorias do Instituto Oswaldo Cruz 2004, 99(5 Suppl 1):63-66.
    82. Reynolds SR, Dahl CE, Harn DA: T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase. J Immunol 1994, 152(1): 193-200.
    83. Reynolds SR, Shoemaker CB, Harn DA: T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni. J Immunol 1992,149(12):3995-4001.
    84. Auriault C, Wolowczuk I, Gras-Masse H, Marguerite M, Boulanger D, Capron A, Tartar A: Epitopic characterization and vaccinal potential of peptides derived from a major antigen of Schistosoma mansoni (Sm28 GST). Peptide research 1991, 4(1):6-11.
    85. Li GF, Wang Y, Zhang ZS, Wang XJ, Ji MJ, Zhu X, Liu F, Cai XP, Wu HW, Wu GL: Identification of immunodominant Th1-type T cell epitopes from Schistosoma japonicum 28 kDa glutathione-S-transferase, a vaccine candidate. Acta biochimica et biophysica Sinica 2005, 37(11):751-758.
    86. Vilar MM, Barrientos F, Almeida M, Thaumaturgo N, Simpson A, Garratt R, Tendler M: An experimental bivalent peptide vaccine against schistosomiasis and fascioliasis. Vaccine 2003, 22(1):137-144.
    87. Fonseca CT, Cunha-Neto E, Goldberg AC, Kalil J, de Jesus AR, Carvalho EM, Correa-Oliveira R, Oliveira SC: Human T cell epitope mapping of the Schistosoma mansoni 14-kDa fatty acid-binding protein using cells from patients living in areas endemic for schistosomiasis. Microbes and infection / Institut Pasteur 2005, 7(2):204-212.
    88. Veprek P, Jezek J, Velek J, Tallima H, Montash M, El Ridi R: Peptides and multiple antigen peptides from Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase: preparation, immunogenicity and immunoprotective capacity in C57BL/6 mice. J Pept Sci 2004, 10(6):350-362.
    89. Argiro L, Henri S, Dessein H, Kouriba B, Dessein AJ, Bourgois A: Induction of a protection against S.mansoni with a MAP containing epitopes of Sm37-GAPDH and Sm10-DLC.Effect of coadsorption with GM-CSF on alum.Vaccine 2000,18(19):2033-2038.
    90.Waine GJ,Mazzer DR,Brandt ER,McManus DP:A dominant B-cell epitope on the 22 kDa tegumental membrane-associated antigen of Schistosoma japonicum maps to an EF-hand calcium binding domain.Parasite immunology 1997,19(8):337-345.
    91.Jankovic D,Aslund L,Oswald IP,Caspar P,Champion C,Pearce E,Coligan JE,Strand M,Sher A,James SL:Calpain is the target antigen of a Th1 clone that transfers protective immunity against Schistosoma ma nsoni.J Immunol 1996,157(2):806-814.
    92.Osada Y,Kumagai T,Hato M,Suzuki T,El-Malky M,Asahi H,Kanazawa T,Ohta N:Establishment of Schistosoma japonicum calpain-specific mouse T cell hybridomas and identification of a T cell epitope that stimulates IFNgamma production.Vaccine 2005,23(21):2813-2819.
    93.el Ridi R,Ozaki T,Sato H,Inaba T,Kamiya H:Immunization of mice with ultraviolet-attenuated cercariae of Schistosoma mansoni transiently reduces the fecundity of challenge worms.International journal for parasitology 1997,27(5):581-586.
    94.Bergquist NR:Schistosomiasis vaccine development:approaches and prospects.Memorias do Instituto Oswaldo Cruz 1995,90(2):221-227.
    95.Pearce EJ,MacDonald AS:The immunobiology of schistosomiasis.Nature reviews 2002,2(7):499-511.
    96.Viyanant V,Upatham ES:Schistosomiasis japonica:epidemiology and genetic aspects.The Southeast Asian journal of tropical medicine and public health 1988,19(1):139-150.
    97.Waine GJ,Becker M,Yang W,Kalinna B,McManus DP:Cloning,molecular characterization,and functional activity of Schistosoma japonicum glyceraldehyde-3-phosphate dehydrogenase,a putative vaccine candidate against schistosomiasis japonica.Infection and immunity 1993,61(11):4716-4723.
    98.Morris GE:Epitope mapping by chemical fragmentation.Methods in molecular biology(Clifton,NJ 1996,66:121-127.
    99.Mazzoni MR,Artemyev NO,Harem HE:Proteolytic fragmentation for epitope mapping.Methods in molecular biology(Clifton,NJ 1996,66:109-120.
    100.Keller PM,Arnold BA,Shaw AR,Tolman RL,Van Middlesworth F,Bondy S,Rusiecki VK,Koenig S,Zolla-Pazner S,Conard Pet al:Identification of HIV vaccine candidate peptides by screening random phage epitope libraries.Virology 1993,193(2):709-716.
    101.Huebener N,Lange B,Lemmel C,Rammensee HG,Strandsby A,Wenkel J,Jikai J,Zeng Y,Gaedicke Ca,Lode HN:Vaccination with minigenes encoding for novel 'self' antigens are effective in DNA-vaccination against neuroblastoma.Cancer letters 2003,197(1-2):211-217.
    102.Pumpens P,Grens E:HBV core particles as a carrier for B cell/T cell epitopes,Intervirology 2001,44(2-3):98-114.
    103.Pearce EJ,C MK,Sun J,J JT,McKee AS,Cervi L:Th2 response polarization during infection with the helminth parasite Schistosoma mansoni.Immunological reviews 2004,201:117-126.
    104.Long M,de Souza SJ,Rosenberg C,Gilbert W:Exon shuffling and the origin of the mitochondrial targeting function in plant cytochrome c1 precursor.Proc Nail Acad Sci U S A 1996,93(15):7727-7731.
    105.Christians FC,Scapozza L,Crameri A,Folkers G,Stemmer WP:Directed evolution of thymidine kinase for AZT phosphorylation using DNA family shuffling.Nat Biotechnol 1999,17(3):259-264.
    106.Hopfner KP,Kopetzki E,Kresse GB,Bode W,Huber R,Engh RA:New enzyme lineages by subdomain shuffling.Proceedings of the National Academy of Sciences of the United States of America 1998,95(17):9813-9818.
    107.Kaessmann H,Zollner S,Nekrutenko A,Li WH:Signatures of domain shuffling in the human genome.Genome Res 2002,12(11):1642-1650.
    108.Zhang YX,Perry K,Vinci VA,Powell K,Stemmer WP,del Cardayre SB:Genome shuffling leads to rapid phenotypic improvement in bacteria.Nature 2002,415(6872):644-646.
    109.Barry MA,Lai WC,Johnston SA:Protection against mycoplasma infection using expression-library immunization.Nature 1995,377(6550):632-635.
    110.Johnston SA,Barry MA:Genetic to genomic vaccination.Vaccine 1997,15(8):808-809.
    111.Smooker PM,Setiady YY,Rainczuk A,Spithill TW:Expression library immunization protects mice against a challenge with virulent rodent malaria.Vaccine 2000,18(23):2533-2540.
    112.Shibui A,Ohmori Y,Suzuki Y,Sasaki M,Nogami S,Sugano S,Watanabe J:Effects of DNA vaccine in murine malaria using a full-length cDNA library.Res Commun Mol Pathol Pharmacol 2001,109(3-4):147-157.
    113.Wu YQ,Ni ZY,Zhang YJ:[Paragonimus Westermani-RNA Extraction and Electrophoretic Analysis].ACTA UNIVERSITATIS MEDICINALIS NANJING 1999,19(4):291-292.
    114.Chen W,Qiu LS:[Schistosoma japonicum adult worm RNA isolation with Chomczynski's method].Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 1993,11(2):135-137.
    115.Cox RA:Structure and function of prokaryotic and eukaryotic ribosomes.Progress in biophysics and molecular biology 1977,32(3):193-231.
    116.Thompson RC:Molecular mimicry in schistosomes.Trends in parasitology 2001,17(4):168.
    117.Pearce EJ,Basch PF,Sher A:Evidence that the reduced surface antigenicity of developing Schistosoma mansoni schistosomula is due to antigen shedding rather than host molecule acquisition.Parasite immunology 1986,8(1):79-94.
    118.Fishelson Z:Novel mechanisms of immune evasion by Schistosoma mansoni.Memorias do Instituto Oswaldo Cruz 1995,90(2):289-292.
    119.Kusel JR,Gordon JF:Biophysical studies of the schistosome surface and their relevance to its properties under immune and drug attack.Parasite immunology 1989,11(5):431-451.
    120.Levy-Holtzman R,Schechter I:Schistosome extracts with heat shock factor activity revealed by the gel shift assay.Parasitology 1994,108(Pt 1):35-42.
    121.Loukas A,Tran M,Pearson MS:Schistosome membrane proteins as vaccines.International journal for parasitology 2007,37(3-4):257-263.
    122.Liu F,Hu W,Cui SJ,Chi M,Fang CY,Wang ZQ,Yang PY,Han ZG:Insight into the host-parasite interplay by proteomic study of host proteins eopurified with the human parasite,Schistosoma japonicum.Proteomics 2007,7(3):450-462.
    123.Kumagai T,Osada Y,Kanazawa T:2-Cys peroxiredoxins from Schistosoma japonicum:the expression profile and localization in the life cycle.Molecular and biochemical parasitology 2006,149(2):135-143.
    124.Wang YY,Liu M,Zhu SC,Ren CP,Shen JJ:[Cloning,Expression and Identification of Membrane Protein Tetraspanin 2-A of Schistosoma japonicum].Zhongguoji sheng chong xue yu ji sheng chong bing za zhi=Chinese journal of parasitology & parasitic diseases 2008,26(1):21-24.
    125.Negroni M,Ricchetti M,Nouvel P,Buc H:Homologous recombination promoted by reverse transcriptase during copying of two distinct RNA templates.Proceedings of the National Academy of Sciences of the United States of America 1995,92(15):6971-6975.
    126.Ouhammouch M,Brody EN:Temperature-dependent template switching during in vitro cDNA synthesis by the AMV-reverse transeriptase.Nucleic acids research 1992,20(20):5443-5450.
    127.Zeng XC,Wang SX:Evidence that BmTXK beta-BmKCT cDNA from Chinese scorpion Buthus martensii Karsch is an artifact generated in the reverse transcription process.FEBS letters 2002,520(1-3):183-184;author reply 185.
    128.Luo GX,Taylor J:Template switching by reverse transeriptase during DNA synthesis.Journal of virology 1990,64(9):4321-4328.
    129.Zhang J,Dean AM,Brunet F,Long M:Evolving protein functional diversity in new genes of Drosophila.Proceedings of the National Academy of Sciences of the United States of America 2004,101(46):16246-16250.
    130.Eichler EE,Sankoff D:Structural dynamics of eukaryotic chromosome evolution.Science(New York,NY 2003,301(5634):793-797.
    131.Zhang JZ:Evolution by gene duplication:an update.TRENDS in Ecology and Evolution 2003,18(6):292-298.
    132.Hemler ME:Tetraspanin functions and associated mierodomains.Nature reviews 2005,6(10):801-811.
    133.Kitadokoro K,Bordo D,Galli G,Petracca R,Falugi F,Abrignani S,Grandi G,Bolognesi M:CD81extracellular domain 3D structure:insight into the tetraspanin superfamily structural motifs.The EMBO journal 2001,20(1-2):12-18.
    134.Stipp CS,Kolesnikova TV,Hemler ME:Functional domains in tetraspanin proteins.Trends in biochemical sciences 2003,28(2):106-112.
    135.Shi P,Zhang J,Yang H,Zhang YP:Adaptive diversification of bitter taste receptor genes in Mammalian evolution.Molecular biology and evolution 2003,20(5):805-814.
    136.Sobhon P,Anupunpisit V,Yuan HC,Upatham ES,Saitongdee P:Schistosoma japonicum (Chinese):changes of the tegument surface in cercariae,scbistosomula and juvenile parasites during development.International journal for parasitology 1988,18(8):1093-1104.
    137.Goldring OL,Clegg JA,Smithers SR,Terry RJ:Acquisition of human blood group antigens by Schistosoma mansoni.Clinical and experimental immunology 1976,26(1):181-187.
    138.Sher A,Hall BF,Vadas MA:Acquisition of murine major histocompatibility complex gene products by schistosomula of Schistosoma mansoni.The Journal of experimental medicine 1978,148(1):46-57.
    139.Torpier G,Capron A,Ouaissi MA:Receptor for IgG(Fc) and human beta2-microglobulin on S.mansoni schistosomula.Nature 1979,278(5703):447-449.
    140.Loukas A,Jones MK,King LT,Brindley PJ,McManus DP:Receptor for Fc on the surfaces of schistosomes.Infection and immunity 2001,69(6):3646-3651.
    141.McIntosh RS,Jones FM,Dunne DW,McKerrow JH,Pleass RJ:Characterization of immunoglobulin binding by schistosomes.Parasite immunology 2006,28(9):407-419.
    142.Yong WK,Das PK:Acquisition of host proteins by the tegument of Schistosoma mansoni recovered from rats.Zeitschrift fur Parasitenkunde(Berlin,Germany) 1983,69(1):53-60.
    143.Kemp WM,Merritt SC,Bogucki MS,Rosier JG,Seed JR:Evidence for adsorption of heterospecific host immunoglobulin on the tegument of Schistosoma mansoni.J Immunol 1977,119(5):1849-1854.
    144.Tarleton RL,Kemp WM:Demonstration of IgG-Fc and C3 receptors on adult Schistosoma mansoni.J Immunol 1981,126(1):379-384.
    145.Santoro F,Ouaissi MA,Pestel J,Capron A:Interaction between Schistosoma mansoni and the complement system:binding of C1q to sehistosomula,J Immunol 1980,124(6):2886-2891.
    146.Modha J,Parikh V,Gauldie J,Doenhoff MJ:An association between schistosomes and contrapsin,a mouse serine proteasc inhibitor(serpin).Parasitology 1988,96(Pt 1):99-109.
    147.Chiang CP,Caulfield JP:The binding of human low-density lipoproteins to the surface of schistosomula of Schistosoma mansoni is inhibited by polyanions and reduces the binding of anti-schistosomal antibodies.The American journal of pathology 1989,134(5):1007-1018.
    148.Damian RT:Molecular mimicry revisited.Parasitology today(Personal ed 1987,3(9):263-266.
    149.Levy S,Shoham T:The tetraspanin web modulates immune-signalling complexes.Nature reviews 2005,5(2):136-148.
    1. WHO: TDR Strategic Direction for Research: Schistosomiasis. Ed, World Health Organization, Geneve 2002.
    2. King CH, Dickman K, Tisch DJ: Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 2005, 365(9470):1561-1569.
    3. Chen MG: Use of praziquantel for clinical treatment and morbidity control of schistosomiasis japonica in China: a review of 30 years' experience. Acta tropica 2005, 96(2-3): 168-176.
    4. Ismail M, Botros S, Metwally A, William S, Farghally A, Tao LF, Day TA, Bennett JL: Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers. The American journal of tropical medicine and hygiene 1999, 60(6):932-935.
    5. Bergquist NR, Leonardo LR, Mitchell GF: Vaccine-linked chemotherapy: can schistosomiasis control benefit from an integrated approach? Trends in parasitology 2005, 21(3): 112-117.
    6. Bergquist NR: Schistosomiasis vaccine development: approaches and prospects. Memorias do Instituto Oswaldo Cruz 1995, 90(2):221-227.
    7. Wu ZD, Lu ZY, Yu XB: Development of a vaccine against Schistosoma japonicum in China: a review. Acta tropica 2005, 96(2-3): 106-116.
    8. Tallima H, Montash M, Veprek P, Velek J, Jezek J, El Ridi R: Differences in immunogenicity and vaccine potential of peptides from Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase. Vaccine 2003, 21(23):3290-3300.
    9. Liu F, Lu J, Hu W, Wang SY, Cui SJ, Chi M, Yan Q, Wang XR, Song HD, Xu XN et al: New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS pathogens 2006, 2(4):e29.
    10. Meyer D, Torres JV: Hypervariable epitope construct: a synthetic immunogen that overcomes MHC restriction of antigen presentation. Mol Immunol 1999,36(10):631-637.
    11. Reynolds SR, Dahl CE, Harn DA: T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase. J Immunol 1994,152(1):193-200.
    12. Arnon R, Tarrab-Hazdai R, Steward M: A mimotope peptide-based vaccine against Schistosoma mansoni: synthesis and characterization. Immunology 2000,101(4):555-562.
    13. Huebener N, Lange B, Lemmel C, Rammensee HG, Strandsby A, Wenkel J, Jikai J, Zeng Y, Gaedicke G, Lode HN: Vaccination with minigenes encoding for novel 'self antigens are effective in DNA-vaccination against neuroblastoma. Cancer letters 2003,197(1-2):211-217.
    14. Williams KM, Bigley EC, 3rd, Raybourne RB: Identification of murine B-cell and T-cell epitopes of Escherichia coli outer membrane protein F with synthetic polypeptides. Infection and immunity 2000, 68(5):2535-2545.
    15. Schirle M, Weinschenk T, Stevanovic S: Combining computer algorithms with experimental approaches permits the rapid and accurate identification of T cell epitopes from defined antigens. Journal of immunological methods 2001, 257( 1 -2): 1-16.
    16. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S: SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 1999, 50(3-4):213-219.
    17. Hagmann M: Computers aid vaccine design. Science (New York, NY2000, 290(5489):80-82.
    18. Gobert GN, Stenzel DJ, Jones MK, Allen DE, McManus DP: Schistosoma japonicum: immunolocalization of paramyosin during development. Parasitology 1997,114 (Pt 1):45-52.
    19. Nara T, Tanabe K, Mahakunkijcharoen Y, Osada Y, Matsumoto N, Kita K, Kojima S: The B cell epitope of paramyosin recognized by a protective monoclonal IgE antibody to Schistosoma japonicum. Vaccine 1997,15(1):79-84.
    20. Fonseca CT, Cunha-Neto E, Kalil J, Jesus AR, Correa-Oliveira R, Carvalho EM, Oliveira SC: Identification of immunodominant epitopes of Schistosoma mansoni vaccine candidate antigens using human T cells. Memorias do Institute Oswaldo Cruz 2004, 99(5 Suppl 1):63-66.
    21. Fonseca CT, Cunha-Neto E, Goldberg AC, Kalil J, de Jesus AR, Carvalho EM, Correa-Oliveira R, Hammer J, Sidney J, Sette A et ah Identification of paramyosin T cell epitopes associated with human resistance to Schistosoma mansoni reinfection. Clinical and experimental immunology 2005,142(3):539-547.
    22. Garcia TC, Fonseca CT, Pacifico LG, Duraes FD, Marinho FA, Penido ML, Caliari MV, de Melo AL, Pinto HA, Barsante MM et al: Peptides containing T cell epitopes, derived from Sm14, but not from paramyosin, induce a Th1 type of immune response, reduction in liver pathology and partial protection against Schistosoma mansoni infection in mice. Acta tropica 2008.
    
    23. Harn DA, Gu W, Oligino LD, Mitsuyama M, Gebremichael A, Richter D: A protective monoclonal antibody specifically recognizes and alters the catalytic activity of schistosome triose-phosphate isomerase. J Immunol 1992,148(2):562-567.
    24. Posnett DN, McGrath H, Tarn JP: A novel method for producing anti-peptide antibodies. Production of site-specific antibodies to the T cell antigen receptor beta-chain. The Journal of biological chemistry 1988, 263(4): 1719-1725.
    25. Gobert GN, Stenzel DJ, McManus DP: Immunolocalisation of the glutathione S-transferases, GST-26 and GST-28, within adult Schistosoma japonicum. International journal for parasitology 1998, 28(9): 1437-1443.
    26. Liu S, Song G, Xu Y, Yang W, McManus DP: Immunization of mice with recombinant Sjc26GST induces a pronounced anti-fecundity effect after experimental infection with Chinese Schistosoma japonicum. Vaccine 1995, 13(6):603-607.
    27. Auriault C, Gras-Masse H, Pierce RJ, Butterworth AE, Wolowczuk I, Capron M, Ouma JH, Balloul JM, Khalife J, Neyrinck JL et ah Antibody response of Schistosoma mansoni-infected human subjects to the recombinant P28 glutathione-S-transferase and to synthetic peptides. Journal of clinical microbiology 1990, 28(9): 1918-1924.
    28. Auriault C, Wolowczuk I, Gras-Masse H, Marguerite M, Boulanger D, Capron A, Tartar A: Epitopic characterization and vaccinal potential of peptides derived from a major antigen of Schistosoma mansoni (Sm28 GST). Peptide research 1991, 4(1):6-11.
    29. Marguerite M, Bossus M, Mazingue C, Wolowczuk I, Gras-Masse H, Tartar A, Capron A, Auriault C: Analysis of antigenicity and immunogenicity of five different chemically defined constructs of a peptide. Mol Immunol 1992, 29(6):793-800.
    30. Xu CB, Verwaerde C, Grzych JM, Fontaine J, Capron A: A monoclonal antibody blocking the Schistosoma mansoni 28-kDa glutathione S-transferase activity reduces female worm fecundity and egg viability. European journal of immunology 1991, 21(8):1801-1807.
    31. Xu CB, Verwaerde C, Gras-Masse H, Fontaine J, Bossus M, Trottein F, Wolowczuk I, Tartar A, Capron A: Schistosoma mansoni 28-kDa glutathione S-transferase and immunity against parasite fecundity and egg viability. Role of the amino- and carboxyl-terminal domains. J Immunol 1993, 150(3):940-949.
    32. Gobert GN, Stenzel DJ, Jones MK, McManus DP: Immunolocalization of the fatty acid-binding protein Sj-FABPc within adult Schistosoma japonicum. Parasitology 1997, 115 ( Pt 1):33-39.
    33. Waine GJ, Scott JC, Mazzer D, McManus DP: Mapping of linear B-cell epitopes on the 14-kDa fatty-acid binding protein of Chinese Schistosoma japonicum. International journal for parasitology 1998,28(2):303-308.
    34. Vilar MM, Barrientos F, Almeida M, Thaumaturgo N, Simpson A, Garratt R, Tendler M: An experimental bivalent peptide vaccine against schistosomiasis and fascioliasis. Vaccine 2003, 22(1):137-144.
    35. Rogers MV, Davern KM, Smythe JA, Mitchell GF: Immunoblotting analysis of the major integral membrane protein antigens of Schistosoma japonicum. Molecular and biochemical parasitology 1988, 29(1):77-87.
    36. Reynolds SR, Shoemaker CB, Harn DA: T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni. J Immunol 1992,149(12):3995-4001.
    37. Brodie AE, Reed DJ: Reversible oxidation of glyceraldehyde 3-phosphate dehydrogenase thiols in human lung carcinoma cells by hydrogen peroxide. Biochemical and biophysical research communications 1987,148(1): 120-125.
    38. Goudot-Crozel V, Caillol D, Djabali M, Dessein AJ: The major parasite surface antigen associated with human resistance to schistosomiasis is a 37-kD glyceraldehyde-3P-dehydrogenase. The Journal of experimental medicine 1989, 170(6):2065-2080.
    39. Dessein AJ, Begley M, Demeure C, Caillol D, Fueri J, dos Reis MG, Andrade ZA, Prata A, Bina JC: Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen. J Immunol 1988, 140(8):2727-2736.
    40. Argiro LL, Kohlstadt SS, Henri SS, Dessein HH, Matabiau VV, Paris PP, Bourgois AA, Dessein AJ: Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH. Vaccine 2000,18(19):2039-2048.
    41. Argiro L, Henri S, Dessein H, Kouriba B, Dessein AJ, Bourgois A: Induction of a protection against S. mansoni with a MAP containing epitopes of Sm37-GAPDH and Sm10-DLC. Effect of coadsorption with GM-CSF on alum. Vaccine2000,18(19):2033-2038.
    42. Waine GJ, Becker M, Yang W, Kalinna B, McManus DP: Cloning, molecular characterization, and functional activity of Schistosoma japonicum glyceraldehyde-3-phosphate dehydrogenase, a putative vaccine candidate against schistosomiasis japonica. Infection and immunity 1993, 61(11):4716-4723.
    1. Hotta H, Ross AH, Huebner K, Isobe M, Wendeborn S, Chao MV, Ricciardi RP, Tsujimoto Y, Croce CM, Koprowski H: Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. Cancer research 1988, 48(11):2955-2962.
    2. Wright MD, Henkle KJ, Mitchell GF: An immunogenic Mr 23,000 integral membrane protein of Schistosoma mansoni worms that closely resembles a human tumor-associated antigen. J Immunol 1990,144(8):3195-3200.
    3. Todres E, Nardi JB, Robertson HM: The tetraspanin superfamily in insects. Insect molecular biology 2000, 9(6):581-590.
    4. Adell T, Gamulin V, Perovic-Ottstadt S, Wiens M, Korzhev M, Muller IM, Muller WE: Evolution of metazoan cell junction proteins: the scaffold protein MAGI and the transmembrane receptor tetraspanin in the demosponge Suberites domuncula. Journal of molecular evolution 2004,59(1):41-50.
    5. Gourgues M, Clergeot PH, Veneault C, Cots J, Sibuet S, Brunet-Simon A, Levis C, Langin T, Lebrun MH: A new class of tetraspanins in fungi. Biochem Biophys Res Commun 2002, 297(5):1197-1204.
    6. Huang S, Yuan S, Dong M, Su J, Yu C, Shen Y, Xie X, Yu Y, Yu X, Chen S et al: The phylogenetic analysis of tetraspanins projects the evolution of cell-cell interactions from unicellular to multicellular organisms. Genomics 2005, 86(6):674-684.
    7. Higginbottom A, Takahashi Y, Boiling L, Coonrod SA, White JM, Partridge LJ, Monk PN: Structural requirements for the inhibitory action of the CD9 large extracellular domain in sperm/oocyte binding and fusion. Biochem Biophys Res Commun 2003,311(1):208-214.
    8. Piled P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G et al: Binding of hepatitis C virus to CD81. Science (New York, NY 1998, 282(5390):938-941.
    9. Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Renia L, Hannoun L, Eling W, Levy S, Boucheix C et al: Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity. Nature medicine 2003, 9(1):93-96.
    10. Hemler ME: Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annual review of cell and developmental biology 2003,19:397-422.
    11. Hemler ME: Specific tetraspanin functions. The Journal of cell biology 2001,155(7):1103-1107.
    12. Kitadokoro K, Bordo D, Galli G, Petracca R, Falugi F, Abrignani S, Grandi G, Bolognesi M: CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs. The EMBO journal 2001, 20(1 -2): 12-18.
    13. Berditchevski F, Odintsova E: Tetraspanins as regulators of protein trafficking. Traffic (Copenhagen, Denmark) 2007, 8(2):89-96.
    14. Hemler ME: Tetraspanin functions and associated mierodomains. Nature reviews 2005, 6(10):801-811.
    15. Rubinstein E, Le Naour F, Lagaudriere-Gesbert C, Billard M, Conjeaud H, Boucheix C: CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. European journal of immunology 1996, 26(11):2657-2665.
    16. Yauch RL, Kazarov AR, Desai B, Lee RT, Hemler ME: Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151. The Journal of biological chemistry 2000, 275(13):9230-9238.
    17. Schick MR, Levy S: The TAPA-1 molecule is associated on the surface of B cells with HLA-DR molecules. J Immunol 1993,151(8):4090-4097.
    18. Szollosi J, Horejsi V, Bene L, Angelisova P, Damjanovich S: Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol 1996, 157(7):2939-2946.
    19. Boucheix C, Rubinstein E: Tetraspanins. Cell Mol Life Sci 2001, 58(9): 1189-1205.
    20. Levy S, Shoham T: Protein-protein interactions in the tetraspanin web. Physiology (Bethesda, Md 2005, 20:218-224.
    21. Kolesnikova TV, Stipp CS, Rao RM, Lane WS, Luscinskas FW, Hemler ME: EWI-2 modulates lymphocyte integrin alpha4beta1 functions. Blood 2004,103(8):3013-3019.
    22. Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E: Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/aIpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. The Biochemical journal 1999, 340 ( Pt 1): 103-111.
    23. Nishiuchi R, Sanzen N, Nada S, Sumida Y, Wada Y, Okada M, Takagi J, Hasegawa H, Sekiguchi K: Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151. Proceedings of the National Academy of Sciences of the United States of America 2005,102(6): 1939-1944.
    24. Kovalenko OV, Yang X, Kolesnikova TV, Hemler ME: Evidence for specific tetraspanin homodimers: inhibition of palmitoylation makes cysteine residues available for cross-linking. The Biochemical journal 2004, 377(Pt 2):407-417.
    25. Liang FX, Riedel I, Deng FM, Zhou G, Xu C, Wu XR, Kong XP, Moll R, Sun TT: Organization of uroplakin subunits: transmembrane topology, pair formation and plaque composition. The Biochemical journal 2001, 355(Pt 1):13-18.
    26. Little KD, Hemler ME, Stipp CS: Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Molecular biology of the cell 2004,15(5):2375-2387.
    27. Zemni R, Bienvenu T, Vinet MC, Sefiani A, Carrie A, Billuart P, McDonell N, Couvert P, Francis F, Chafey P et al: A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation. Nature genetics 2000, 24(2): 167-170.
    28. Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, Brady RL, Daniels G, Anstee DJ: CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood 2004,104(8):2217-2223.
    29. Kagan A, Feld S, Chemke J, Bar-Khayim Y: Occurrence of hereditary nephritis, pretibial epidermolysis bullosa and beta-thalassemia minor in two siblings with end-stage renal disease. Nephron 1988, 49(4):331-332.
    30. Kohl S, Giddings I, Besch D, Apfelstedt-Sylla E, Zrenner E, Wissinger B: The role of the peripherin/RDS gene in retinal dystrophies. Acta anatomica 1998,162(2-3):75-84.
    31. Dryja TP, Hahn LB, Kajiwara K, Berson EL: Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa. Investigative ophthalmology & visual science 1997, 38(10):1972-1982.
    32. Kajiwara K, Berson EL, Dryja TP: Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science (New York, NY 1994, 264(5165): 1604-1608.
    33. Kaji K, Oda S, Shikano T, Ohnuki T, Uematsu Y, Sakagami J, Tada N, Miyazaki S, Kudo A: The gamete fusion process is defective in eggs of Cd9-deficient mice. Nature genetics 2000, 24(3):279-282.
    34. Le Naour F, Rubinstein E, Jasmin C, Prenant M, Boucheix C: Severely reduced female fertility in CD9-deficient mice. Science (New York, NY 2000, 287(5451):319-321.
    35. Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, Suzuki K, Kosai K, Inoue K, Ogura A et al: Requirement of CD9 on the egg plasma membrane for fertilization. Science (New York, NY 2000, 287(5451):321-324.
    36. Takeda Y, Tachibana I, Miyado K, Kobayashi M, Miyazaki T, Funakoshi T, Kimura H, Yamane H, Saito Y, Goto H et al: Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. The Journal of cell biology 2003,161(5):945-956.
    37. Ishibashi T, Ding L, Ikenaka K, Inoue Y, Miyado K, Mekada E, Baba H: Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation. J Neurosci 2004, 24(1):96-102.
    38. Maecker HT, Levy S: Normal lymphocyte development but delayed humoral immune response in CD81-null mice. The Journal of experimental medicine 1997,185(8):1505-1510.
    39. Tsitsikov EN, Gutierrez-Ramos JC, Geha RS: Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 1997, 94(20): 10844-10849.
    40. Geisert EE, Jr., Williams RW, Geisert GR, Fan L, Asbury AM, Maecker HT, Deng J, Levy S: Increased brain size and glial cell number in CD81-null mice. The Journal of comparative neurology 2002, 453(1):22-32.
    41. Miyazaki T, Muller U, Campbell KS: Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. The EMBO journal 1997, 16(14):4217-4225.
    42. van Spriel AB, Puls KL, Sofi M, Pouniotis D, Hochrein H, Orinska Z, Knobeloch KP, Plebanski M, Wright MD: A regulatory role for CD37 in T cell proliferation. J Immunol 2004, 172(5):2953-2961.
    43. Knobeloch KP, Wright MD, Ochsenbein AF, Liesenfeld O, Lohler J, Zinkernagel RM, Horak I, Orinska Z: Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions. Molecular and cellular biology 2000, 20(15):5363-5369.
    44. Tarrant JM, Groom J, Metcalf D, Li R, Borobokas B, Wright MD, Tarlinton D, Robb L: The absence of Tssc6, a member of the tetraspanin superfamily, does not affect lymphoid development but enhances in vitro T-cell proliferative responses. Molecular and cellular biology 2002,22(14):5006-5018.
    45. Lau LM, Wee JL, Wright MD, Moseley GW, Hogarth PM, Ashman LK, Jackson DE: The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function. Blood 2004,104(8):2368-2375.
    46. Wright MD, Geary SM, Fitter S, Moseley GW, Lau LM, Sheng KC, Apostolopoulos V, Stanley EG, Jackson DE, Ashman LK: Characterization of mice lacking the tetraspanin superfamily member CD151. Molecular and cellular biology 2004, 24(13):5978-5988.
    47. Connell G, Bascom R, Molday L, Reid D, McInnes RR, Molday RS: Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse. Proceedings of the National Academy of Sciences of the United States of America 1991, 88(3):723-726.
    48. Clarke G, Goldberg AF, Vidgen D, Collins L, Ploder L, Schwarz L, Molday LL, Rossant J, Szel A, Molday RS et al: Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nature genetics 2000, 25(1):67-73.
    49. Kopczynski CC, Davis GW, Goodman CS: A neural tetraspanin, encoded by late bloomer, that facilitates synapse formation. Science (New York, NY 1996, 271(5257): 1867-1870.
    50. Xu H, Lee SJ, Suzuki E, Dugan KD, Stoddard A, Li HS, Chodosh LA, Montell C: A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen. The EMBO journal 2004, 23(4):811-822.
    51. Sinenko SA, Mathey-Prevot B: Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes. Oncogene 2004, 23(56):9120-9128.
    52. Moribe H, Yochem J, Yamada H, Tabuse Y, Fujimoto T, Mekada E: Tetraspanin protein (TSP-15) is required for epidermal integrity in Caenorhabditis elegans. Journal of cell science 2004, 117(Pt 22):5209-5220.
    
    53. Clergeot PH, Gourgues M, Cots J, Laurans F, Latorse MP, Pepin R, Tharreau D, Notteghem JL, Lebrun MH: PLS1, a gene encoding a tetraspanin-like protein, is required for penetration of rice leaf by the fungal pathogen Magnaporthe grisea. Proceedings of the National Academy of Sciences of the United States of America 2001, 98(12):6963-6968.
    54. Gourgues M, Brunet-Simon A, Lebrun MH, Levis C: The tetraspanin BcPlsl is required for appressorium-mediated penetration of Botrytis cinerea into host plant leaves. Molecular microbiology 2004, 51(3):619-629.
    55. Veneault-Fourrey C, Parisot D, Gourgues M, Lauge R, Lebrun MH, Langin T: The tetraspanin gene C1PLS1 is essential for appressorium-mediated penetration of the fungal pathogen Colletotrichum lindemuthianum. Fungal Genet Biol 2005, 42(4):306-318.
    56. Waterhouse R, Ha C, Dveksler GS: Murine CD9 is the receptor for pregnancy-specific glycoprotein 17. The Journal of experimental medicine 2002, 195(2):277-282.
    57. Rubinstein E, Ziyyat A, Prenant M, Wrobel E, Wolf JP, Levy S, Le Naour F, Boucheix C: Reduced fertility of female mice lacking CD81. Developmental biology 20%, 290(2):351-358.
    58. Tanigawa M, Miyamoto K, Kobayashi S, Sato M, Akutsu H, Okabe M, Mekada E, Sakakibara K, Miyado M, Umezawa A et al: Possible involvement of CD81 in acrosome reaction of sperm in mice. Mol Reprod Dev 2007.
    59. Sachs N, Kreft M, van den Bergh Weerman MA, Beynon AJ, Peters TA, Weening JJ, Sonnenberg A: Kidney failure in mice lacking the tetraspanin CD151. The Journal of cell biology 2006, 175(1):33-39.
    
    60. von Lindern JJ, Rojo D, Grovit-Ferbas K, Yeramian C, Deng C, Herbein G, Ferguson MR, Pappas TC, Decker JM, Singh A et al: Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages. Journal of virology 2003, 77(6):3624-3633.
    61. Cherukuri A, Shoham T, Sohn HW, Levy S, Brooks S, Carter R, Pierce SK: The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts. J Immunol 2004, 172(1):370-380.
    62. Levy S, Shoham T: The tetraspanin web modulates immune-signalling complexes. Nat Rev Immunol 2005, 5(2): 136-148.
    63. Meyer-Wentrup F, Figdor CG, Ansems M, Brossart P, Wright MD, Adema GJ, van Spriel AB: Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production. J Immunol 2007, 178(1):154-162.
    64. Winterwood NE, Varzavand A, Meland MN, Ashman LK, Stipp CS: A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. Molecular biology of the cell 2006, 17(6):2707-2721.
    65. Rous BA, Reaves BJ, Ihrke G, Briggs JA, Gray SR, Stephens DJ, Banting G, Luzio JP: Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes. Molecular biology of the cell2002, 13(3):1071-1082.
    66. Duffield A, Kamsteeg EJ, Brown AN, Pagel P, Caplan MJ: The tetraspanin CD63 enhances the internalization of the H,K-ATPase beta-subunit. Proceedings of the National Academy of Sciences of the United States of America 2003, 100(26):15560-15565.
    67. Hammond C, Denzin LK, Pan M, Griffith JM, Geuze HJ, Cresswell P: The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules. J Immunol 1998, 161(7):3282-3291.
    68. Delaguillaumie A, Harriague J, Kohanna S, Bismuth G, Rubinstein E, Seigneuret M, Conjeaud H: Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation. Journal of cell science 2004, 117(Pt22):5269-5282.
    69. Odintsova E, Voortman J, Gilbert E, Berditchevski F: Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. Journal of cell science 2003, 116(Pt 22):4557-4566.

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