Research status and prospect of echinococcosis<b>-</b>specific vaccine antigens_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANG Xianwei ¹ , TAO Lang ^1,2 , WEI Jinwen ² , LIU Jinxian ²

1. Department of Thyroid Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China;
2. School of Medicine, University of Electronic Science and Technology of China, Chengdu 610056, P. R. China;

Corresponding author：

YANG Xianwei, Email: yxwdocor@163.com

Keywords：

hydatid disease; vaccine; Eg95 protein; gene recombination; antigen

DOI：

10.7507/1007-9424.202212066

Video：

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Objective To summarize the research status of echinococcosis- specific vaccine antigens, analyze their sources and application prospects, and to provide new ideas for the development of echinococcosis vaccine antigens and drug treatment. Method Research on echinococcosis-specific vaccine antigens at home and abroad was searched and reviewed. Results Natural hydatid antigens, such as cystic fluid crude antigen, protoscolex segment, germinal layer, etc. often appear due to the difficulty of material acquisition and cumbersome preparation, resulting in unstable evaluation indicators such as sensitivity and specificity. The gene or protein sequences of a new recombinant hydatid antigen was accessible, the reproducibility and specificity were better, and it was more suitable for batch production testing, which was the main direction of current research, such as rAgB8/1, rEm18, rEm2, etc. Conclusions Vaccine development is one of the main directions for the elimination of hydatidosis. In the interaction between echinococcus and human or animal hosts, the natural structural proteins or excretion/secretion proteins of echinococcus stimulate the host to produce anti-parasites immunity and immune clearance, and the search for these specific protein antigens is of great significance for vaccine development, and new drug treatment.

Citation： YANG Xianwei, TAO Lang, WEI Jinwen, LIU Jinxian. Research status and prospect of echinococcosis-specific vaccine antigens. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(6): 734-738. doi: 10.7507/1007-9424.202212066 Copy

1.	Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev, 2019, 32(2): e00075-18. doi: 10.1128/CMR.00075-18.
2.	Yang X, Qiu Y, Huang B, et al. Novel techniques and preliminary results of ex vivo liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis: A study of 31 cases. Am J Transplant, 2018, 18(7): 1668-1679.
3.	Qiu Y, Huang B, Yang X, et al. Evaluating the benefits and risks of ex vivo liver resection and autotransplantation in treating hepatic end-stage alveolar echinococcosis. Clin Infect Dis, 2022, 75(8): 1289-1296.
4.	McManus DP, Gray DJ, Zhang W, et al. Diagnosis, treatment, and management of echinococcosis. BMJ, 2012, 344: e3866. doi: 10.1136/bmj.e3866.
5.	韩帅, 蒉嫣, 薛垂召, 等. 2004-2020年全国棘球蚴病疫情分析. 中国寄生虫学与寄生虫病杂志, 2022, 40(4): 475-480.
6.	廖沙, 王奇, 杨柳, 等. 2020年四川省包虫病监测结果分析. 预防医学情报杂志, 2021, 37(12): 1641-1647.
7.	魏玉环, 胡媛, 曹建平. 抗细粒棘球绦虫疫苗的研究进展. 中国寄生虫学与寄生虫病杂志, 2019, 37(1): 97-101.
8.	徐偲瑜, 唐丹. 新型冠状病毒疫苗及抗体药物研发进展. 生物医学工程学杂志, 2022, 39(5): 1059-1064.
9.	Kandil OM, Abdelrahman KA, Mahmoud MS, et al. Cystic echinococcosis: development of an intermediate host rabbit model for using in vaccination studies. Exp Parasitol, 2020, 208: 107800. doi: 10.1016/j.exppara.2019.107800.
10.	Ran B, Shao Y, Guo Y, et al. Surgical treatment of hepatic cystic echinococcosis in patients co-infected with HIV/AIDS. J Helminthol, 2016, 90(1): 125-128.
11.	Chen X, Chen X, Shao Y, et al. Clinical outcome and immune follow-up of different surgical approaches for human cyst hydatid disease in liver. Am J Trop Med Hyg, 2014, 91(4): 801-805.
12.	Zhou Z, Zhou P, Mu Y, et al. Therapeutic effect on alveolar echinococcosis by targeting EM-leucine aminopeptidase. Front Immunol, 2022, 13: 1027500. doi: 10.3389/fimmu.2022.1027500.
13.	Chen L, Cheng Z, Xian S, et al. Immunization with Em CRT-induced protective immunity against echinococcus multilocularis infection in BALB/c mice. Trop Med Infect Dis, 2022, 7(10): 279. doi: 10.3390/tropicalmed7100279.
14.	Labanchi JL, Poggio TV, Gutierrez A, et al. Analysis of vaccination strategy against cystic echinococcosis developed in the province of Rio Negro, Argentina: 12 years of work. Vet Parasitol, 2022, 310: 109790. doi: 10.1016/j.vetpar.2022.109790.
15.	Gadicke P, Heath D, Medina-Brunet A, et al. Assessment of the vaccination program against cystic echinococcosis in sheep in the pehuenche community of central Chile. Animals (Basel), 2022, 12(6): 679. doi: 10.3390/ani12060679.
16.	Xu T, Liu L, Shi C, et al. A recombinant rabies virus expressing Echinococcus granulosus EG95 induces protective immunity in mice. Transbound Emerg Dis, 2022, 69(4): e254-e266. doi: 10.1111/tbed.14292.
17.	Gauci CG, Jenkins DJ, Lightowlers MW. Protection against cystic echinococcosis in sheep using an Escherichia coli-expressed recombinant antigen (EG95) as a bacterin. Parasitology, 2022: 1-3.
18.	Kronenberg PA, Deibel A, Gottstein B, et al. Serological assays for alveolar and cystic echinococcosis-a comparative multi-test study in Switzerland and Kyrgyzstan. Pathogens, 2022, 11(5): 518. doi: 10.3390/pathogens11050518.
19.	Gauci C, Merli M, Muller V, et al. Molecular cloning of a vaccine antigen against infection with the larval stage of Echinococcus multilocularis. Infect Immun, 2002, 70(7): 3969-3972.
20.	Wang H, Zhang F, Ma X, et al. Prokaryotic expression and identification of B- and T-cell combined epitopes of Em95 antigen of Echinococcus multilocularis. Int J Clin Exp Pathol, 2014, 7(8): 5117-5122.
21.	Fu Y, Martinez C, Chalar C, et al. A new potent antigen from Echinococcus granulosus associated with muscles and tegument. Mol Biochem Parasitol, 1999, 102(1): 43-52.
22.	叶艳菊, 李文桂. 细粒棘球绦虫Eg95-EgA31融合基因苜蓿叶蛋白提取液诱导小鼠细胞因子的变化. 中国寄生虫学与寄生虫病杂志, 2010, 28(2): 94-97.
23.	Li Y, Zhu Y, Sha T, et al. A multi-epitope chitosan nanoparticles vaccine of canine against echinococcus granulosus. J Biomed Nanotechnol, 2021, 17(5): 910-920.
24.	Katoh Y, Kouguchi H, Matsumoto J, et al. Characterization of emY162 encoding an immunogenic protein cloned from an adult worm-specific cDNA library of Echinococcus multilocularis. Biochim Biophys Acta, 2008, 1780(1): 1-6.
25.	格日力, 汤锋, 李润乐, 等. 多房棘球蚴终末宿主犬亚单位疫苗LTB-EMY162的免疫原性及免疫效果评价. 青海大学, 2020.
26.	曹春宝, 马秀敏, 丁剑冰, 等. 细粒棘球绦虫egG1Y162抗原基因的克隆及序列分析. 中国寄生虫学与寄生虫病杂志, 2009, 27(2): 177-179.
27.	Ma X, Zhao H, Zhang F, et al. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection. Hum Vaccin Immunother, 2016, 12(1): 170-175.
28.	Teichmann A, Vargas DM, Monteiro KM, et al. Characterization of 14-3-3 isoforms expressed in the Echinococcus granulosus pathogenic larval stage. J Proteome Res, 2015, 14(4): 1700-1715.
29.	Pourseif MM, Moghaddam G, Nematollahi A, et al. Vaccination with rEGVac elicits immunoprotection against different stages of Echinococcus granulosus life cycle: A pilot study. Acta Trop, 2021, 218: 105883. doi: 10.1016/j.actatropica.2021.105883.
30.	Lampe K, Gottstein B, Becker T, et al. Immunization of rhesus macaques with Echinococcus multilocularis recombinant 14-3-3 antigen leads to specific antibody response. Parasitol Res, 2017, 116(1): 435-439.
31.	郭宝平, 张壮志, 古努尔·吐尔逊, 等. EgM9免疫犬产生抗体变化规律的观察. 中国人兽共患病学报, 2010, 26(4): 325-329.
32.	Zhang ZZ, Guo G, Li J, et al. Dog vaccination with EgM proteins against Echinococcus granulosus. Infect Dis Poverty, 2018, 7(1): 61. doi: 10.1186/s40249-018-0425-4.
33.	Masih Z, Hoghooghirad N, Madani R, et al. Expression and production of protoscolex recombinant P29 protein and its serological evaluation for diagnosis of human hydatidosis. J Parasit Dis, 2022, 46(2): 377-383.
34.	Xian J, Zhao P, Wang N, et al. Molecular characterization of a tetraspanin TSP11 gene in echinococcus granulosus and evaluation its immunoprotection in model dogs. Front Vet Sci, 2021, 8: 759283. doi: 10.3389/fvets.2021.759283.
35.	Lv Y, Zhu Y, Chang L, et al. Identification of a dominant murine T-cell epitope in recombinant protein P29 from Echinococcus granulosus. Acta Biochim Biophys Sin (Shanghai), 2022, 54(4): 482-493.
36.	Chabalgoity JA, Moreno M, Carol H, et al. Salmonella typhimurium as a basis for a live oral Echinococcus granulosus vaccine. Vaccine, 2000, 19(4-5): 460-469.
37.	Anvari D, Rezaei F, Ashouri A, et al. Current situation and future prospects of Echinococcus granulosus vaccine candidates: A systematic review. Transbound Emerg Dis, 2021, 68(3): 1080-1096.
38.	李航, 滕飞, 孔庆研, 等. 分期切除术治疗多病灶复杂肝泡型包虫病. 中国普外基础与临床杂志, 2023, 30(1): 43-47.
39.	杨文昊, 廖玉波, 黄良, 等. “在体优先”的离体肝切除联合自体肝移植术治疗晚期肝泡型包虫病的应用效果. 中国普外基础与临床杂志, 2022, 29(10): 1308-1312.
40.	杨令鹏, 邱逸闻, 杨先伟, 等. 泡型肝包虫病手术安全切除距离的初步研究. 中国普外基础与临床杂志, 2022, 29(4): 512-516.
41.	Lass A, Szostakowska B, Kontogeorgos I, et al. First detection of Echinococcus multilocularis in environmental water sources in endemic areas using capsule filtration and molecular detection methods. Water Res, 2019, 160: 466-474.

1. Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev, 2019, 32(2): e00075-18. doi: 10.1128/CMR.00075-18.
2. Yang X, Qiu Y, Huang B, et al. Novel techniques and preliminary results of ex vivo liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis: A study of 31 cases. Am J Transplant, 2018, 18(7): 1668-1679.
3. Qiu Y, Huang B, Yang X, et al. Evaluating the benefits and risks of ex vivo liver resection and autotransplantation in treating hepatic end-stage alveolar echinococcosis. Clin Infect Dis, 2022, 75(8): 1289-1296.
4. McManus DP, Gray DJ, Zhang W, et al. Diagnosis, treatment, and management of echinococcosis. BMJ, 2012, 344: e3866. doi: 10.1136/bmj.e3866.
5. 韩帅, 蒉嫣, 薛垂召, 等. 2004-2020年全国棘球蚴病疫情分析. 中国寄生虫学与寄生虫病杂志, 2022, 40(4): 475-480.
6. 廖沙, 王奇, 杨柳, 等. 2020年四川省包虫病监测结果分析. 预防医学情报杂志, 2021, 37(12): 1641-1647.
7. 魏玉环, 胡媛, 曹建平. 抗细粒棘球绦虫疫苗的研究进展. 中国寄生虫学与寄生虫病杂志, 2019, 37(1): 97-101.
8. 徐偲瑜, 唐丹. 新型冠状病毒疫苗及抗体药物研发进展. 生物医学工程学杂志, 2022, 39(5): 1059-1064.
9. Kandil OM, Abdelrahman KA, Mahmoud MS, et al. Cystic echinococcosis: development of an intermediate host rabbit model for using in vaccination studies. Exp Parasitol, 2020, 208: 107800. doi: 10.1016/j.exppara.2019.107800.
10. Ran B, Shao Y, Guo Y, et al. Surgical treatment of hepatic cystic echinococcosis in patients co-infected with HIV/AIDS. J Helminthol, 2016, 90(1): 125-128.
11. Chen X, Chen X, Shao Y, et al. Clinical outcome and immune follow-up of different surgical approaches for human cyst hydatid disease in liver. Am J Trop Med Hyg, 2014, 91(4): 801-805.
12. Zhou Z, Zhou P, Mu Y, et al. Therapeutic effect on alveolar echinococcosis by targeting EM-leucine aminopeptidase. Front Immunol, 2022, 13: 1027500. doi: 10.3389/fimmu.2022.1027500.
13. Chen L, Cheng Z, Xian S, et al. Immunization with Em CRT-induced protective immunity against echinococcus multilocularis infection in BALB/c mice. Trop Med Infect Dis, 2022, 7(10): 279. doi: 10.3390/tropicalmed7100279.
14. Labanchi JL, Poggio TV, Gutierrez A, et al. Analysis of vaccination strategy against cystic echinococcosis developed in the province of Rio Negro, Argentina: 12 years of work. Vet Parasitol, 2022, 310: 109790. doi: 10.1016/j.vetpar.2022.109790.
15. Gadicke P, Heath D, Medina-Brunet A, et al. Assessment of the vaccination program against cystic echinococcosis in sheep in the pehuenche community of central Chile. Animals (Basel), 2022, 12(6): 679. doi: 10.3390/ani12060679.
16. Xu T, Liu L, Shi C, et al. A recombinant rabies virus expressing Echinococcus granulosus EG95 induces protective immunity in mice. Transbound Emerg Dis, 2022, 69(4): e254-e266. doi: 10.1111/tbed.14292.
17. Gauci CG, Jenkins DJ, Lightowlers MW. Protection against cystic echinococcosis in sheep using an Escherichia coli-expressed recombinant antigen (EG95) as a bacterin. Parasitology, 2022: 1-3.
18. Kronenberg PA, Deibel A, Gottstein B, et al. Serological assays for alveolar and cystic echinococcosis-a comparative multi-test study in Switzerland and Kyrgyzstan. Pathogens, 2022, 11(5): 518. doi: 10.3390/pathogens11050518.
19. Gauci C, Merli M, Muller V, et al. Molecular cloning of a vaccine antigen against infection with the larval stage of Echinococcus multilocularis. Infect Immun, 2002, 70(7): 3969-3972.
20. Wang H, Zhang F, Ma X, et al. Prokaryotic expression and identification of B- and T-cell combined epitopes of Em95 antigen of Echinococcus multilocularis. Int J Clin Exp Pathol, 2014, 7(8): 5117-5122.
21. Fu Y, Martinez C, Chalar C, et al. A new potent antigen from Echinococcus granulosus associated with muscles and tegument. Mol Biochem Parasitol, 1999, 102(1): 43-52.
22. 叶艳菊, 李文桂. 细粒棘球绦虫Eg95-EgA31融合基因苜蓿叶蛋白提取液诱导小鼠细胞因子的变化. 中国寄生虫学与寄生虫病杂志, 2010, 28(2): 94-97.
23. Li Y, Zhu Y, Sha T, et al. A multi-epitope chitosan nanoparticles vaccine of canine against echinococcus granulosus. J Biomed Nanotechnol, 2021, 17(5): 910-920.
24. Katoh Y, Kouguchi H, Matsumoto J, et al. Characterization of emY162 encoding an immunogenic protein cloned from an adult worm-specific cDNA library of Echinococcus multilocularis. Biochim Biophys Acta, 2008, 1780(1): 1-6.
25. 格日力, 汤锋, 李润乐, 等. 多房棘球蚴终末宿主犬亚单位疫苗LTB-EMY162的免疫原性及免疫效果评价. 青海大学, 2020.
26. 曹春宝, 马秀敏, 丁剑冰, 等. 细粒棘球绦虫egG1Y162抗原基因的克隆及序列分析. 中国寄生虫学与寄生虫病杂志, 2009, 27(2): 177-179.
27. Ma X, Zhao H, Zhang F, et al. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection. Hum Vaccin Immunother, 2016, 12(1): 170-175.
28. Teichmann A, Vargas DM, Monteiro KM, et al. Characterization of 14-3-3 isoforms expressed in the Echinococcus granulosus pathogenic larval stage. J Proteome Res, 2015, 14(4): 1700-1715.
29. Pourseif MM, Moghaddam G, Nematollahi A, et al. Vaccination with rEGVac elicits immunoprotection against different stages of Echinococcus granulosus life cycle: A pilot study. Acta Trop, 2021, 218: 105883. doi: 10.1016/j.actatropica.2021.105883.
30. Lampe K, Gottstein B, Becker T, et al. Immunization of rhesus macaques with Echinococcus multilocularis recombinant 14-3-3 antigen leads to specific antibody response. Parasitol Res, 2017, 116(1): 435-439.
31. 郭宝平, 张壮志, 古努尔·吐尔逊, 等. EgM9免疫犬产生抗体变化规律的观察. 中国人兽共患病学报, 2010, 26(4): 325-329.
32. Zhang ZZ, Guo G, Li J, et al. Dog vaccination with EgM proteins against Echinococcus granulosus. Infect Dis Poverty, 2018, 7(1): 61. doi: 10.1186/s40249-018-0425-4.
33. Masih Z, Hoghooghirad N, Madani R, et al. Expression and production of protoscolex recombinant P29 protein and its serological evaluation for diagnosis of human hydatidosis. J Parasit Dis, 2022, 46(2): 377-383.
34. Xian J, Zhao P, Wang N, et al. Molecular characterization of a tetraspanin TSP11 gene in echinococcus granulosus and evaluation its immunoprotection in model dogs. Front Vet Sci, 2021, 8: 759283. doi: 10.3389/fvets.2021.759283.
35. Lv Y, Zhu Y, Chang L, et al. Identification of a dominant murine T-cell epitope in recombinant protein P29 from Echinococcus granulosus. Acta Biochim Biophys Sin (Shanghai), 2022, 54(4): 482-493.
36. Chabalgoity JA, Moreno M, Carol H, et al. Salmonella typhimurium as a basis for a live oral Echinococcus granulosus vaccine. Vaccine, 2000, 19(4-5): 460-469.
37. Anvari D, Rezaei F, Ashouri A, et al. Current situation and future prospects of Echinococcus granulosus vaccine candidates: A systematic review. Transbound Emerg Dis, 2021, 68(3): 1080-1096.
38. 李航, 滕飞, 孔庆研, 等. 分期切除术治疗多病灶复杂肝泡型包虫病. 中国普外基础与临床杂志, 2023, 30(1): 43-47.
39. 杨文昊, 廖玉波, 黄良, 等. “在体优先”的离体肝切除联合自体肝移植术治疗晚期肝泡型包虫病的应用效果. 中国普外基础与临床杂志, 2022, 29(10): 1308-1312.
40. 杨令鹏, 邱逸闻, 杨先伟, 等. 泡型肝包虫病手术安全切除距离的初步研究. 中国普外基础与临床杂志, 2022, 29(4): 512-516.
41. Lass A, Szostakowska B, Kontogeorgos I, et al. First detection of Echinococcus multilocularis in environmental water sources in endemic areas using capsule filtration and molecular detection methods. Water Res, 2019, 160: 466-474.

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Research status and prospect of echinococcosis-specific vaccine antigens

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