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.	韓帥, 蕢嫣, 薛垂召, 等. 2004-2020年全國棘球蚴病疫情分析. 中國寄生蟲學與寄生蟲病雜志, 2022, 40(4): 475-480.
6.	廖沙, 王奇, 楊柳, 等. 2020年四川省包蟲病監測結果分析. 預防醫學情報雜志, 2021, 37(12): 1641-1647.
7.	魏玉環, 胡媛, 曹建平. 抗細粒棘球絳蟲疫苗的研究進展. 中國寄生蟲學與寄生蟲病雜志, 2019, 37(1): 97-101.
8.	徐偲瑜, 唐丹. 新型冠狀病毒疫苗及抗體藥物研發進展. 生物醫學工程學雜志, 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.	葉艷菊, 李文桂. 細粒棘球絳蟲Eg95-EgA31融合基因苜蓿葉蛋白提取液誘導小鼠細胞因子的變化. 中國寄生蟲學與寄生蟲病雜志, 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, 湯鋒, 李潤樂, 等. 多房棘球蚴終末宿主犬亞單位疫苗LTB-EMY162的免疫原性及免疫效果評價. 青海大學, 2020.
26.	曹春寶, 馬秀敏, 丁劍冰, 等. 細粒棘球絳蟲egG1Y162抗原基因的克隆及序列分析. 中國寄生蟲學與寄生蟲病雜志, 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.	郭寶平, 張壯志, 古努爾·吐爾遜, 等. EgM9免疫犬產生抗體變化規律的觀察. 中國人獸共患病學報, 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, 滕飛, 孔慶研, 等. 分期切除術治療多病灶復雜肝泡型包蟲病. 中國普外基礎與臨床雜志, 2023, 30(1): 43-47.
39.	楊文昊, 廖玉波, 黃良, 等. “在體優先”的離體肝切除聯合自體肝移植術治療晚期肝泡型包蟲病的應用效果. 中國普外基礎與臨床雜志, 2022, 29(10): 1308-1312.
40.	楊令鵬, 邱逸聞, 楊先偉, 等. 泡型肝包蟲病手術安全切除距離的初步研究. 中國普外基礎與臨床雜志, 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. 韓帥, 蕢嫣, 薛垂召, 等. 2004-2020年全國棘球蚴病疫情分析. 中國寄生蟲學與寄生蟲病雜志, 2022, 40(4): 475-480.
6. 廖沙, 王奇, 楊柳, 等. 2020年四川省包蟲病監測結果分析. 預防醫學情報雜志, 2021, 37(12): 1641-1647.
7. 魏玉環, 胡媛, 曹建平. 抗細粒棘球絳蟲疫苗的研究進展. 中國寄生蟲學與寄生蟲病雜志, 2019, 37(1): 97-101.
8. 徐偲瑜, 唐丹. 新型冠狀病毒疫苗及抗體藥物研發進展. 生物醫學工程學雜志, 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. 葉艷菊, 李文桂. 細粒棘球絳蟲Eg95-EgA31融合基因苜蓿葉蛋白提取液誘導小鼠細胞因子的變化. 中國寄生蟲學與寄生蟲病雜志, 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, 湯鋒, 李潤樂, 等. 多房棘球蚴終末宿主犬亞單位疫苗LTB-EMY162的免疫原性及免疫效果評價. 青海大學, 2020.
26. 曹春寶, 馬秀敏, 丁劍冰, 等. 細粒棘球絳蟲egG1Y162抗原基因的克隆及序列分析. 中國寄生蟲學與寄生蟲病雜志, 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. 郭寶平, 張壯志, 古努爾·吐爾遜, 等. EgM9免疫犬產生抗體變化規律的觀察. 中國人獸共患病學報, 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, 滕飛, 孔慶研, 等. 分期切除術治療多病灶復雜肝泡型包蟲病. 中國普外基礎與臨床雜志, 2023, 30(1): 43-47.
39. 楊文昊, 廖玉波, 黃良, 等. “在體優先”的離體肝切除聯合自體肝移植術治療晚期肝泡型包蟲病的應用效果. 中國普外基礎與臨床雜志, 2022, 29(10): 1308-1312.
40. 楊令鵬, 邱逸聞, 楊先偉, 等. 泡型肝包蟲病手術安全切除距離的初步研究. 中國普外基礎與臨床雜志, 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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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research status and prospect of echinococcosis-specific vaccine antigens

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