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Production and Evaluation of a Novel Multi-Epitope Bivalent Vaccine Against Echinococcus multilocaularis Metacestode

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Abstract

Alveolar Echinococcosis is a globally widespread zoonotic disease caused by the larval stage of Echinococcus multilocularis (Em) and is seriously harmful to human health. In our previous studies, we found that Em-EMY162 had good prophylactic and therapeutic effects against Em infection and the dominant epitopes of Em-EMY162 and Em-TSP3 were also identified. In this study, a multi-epitope vaccine LTB-ETBM targeting both Em-EMY162 and Em-TSP3 was designed and constructed, and then the immunogenicity and protective efficacy were evaluated in Em infected mice. The results showed that LTB-ETBM could induce high levels of specific IgG against Em-EMY162 and Em-TSP3 and a mixed Th1/Th2 lymphocyte response to LTB-ETBM. Moreover, the LTB-ETBM significantly inhibited the formation of cysts in mice challenged with 1000 Em protoscoleces. In a therapeutic mouse model injected intraperitoneally with 1000 protoscoleces, vaccination with LTB-ETBM using either Freund's or CpG as an adjuvant significantly decreased the growth of protoscoleces and the formation of cysts. LTB-ETBM may be efficacious for use as a prophylactic or therapeutic agent against Em infection.

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References

  • Atanasov G, Benckert C, Thelen A, Tappe D, Frosch M, Teichmann D, Barth TF, Wittekind C, Schubert S, Jonas S (2013) Alveolar echinococcosis-spreading disease challenging clinicians: a case report and literature review. World J Gastroenterol: WJG 19(26):4257

    Article  Google Scholar 

  • Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM (2011) CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 10(4):499–511

    Article  CAS  Google Scholar 

  • Boubaker G, Hemphill A, Huber CO, Spiliotis M, Babba H, Gottstein B (2015) Prevention and immunotherapy of secondary murine alveolar echinococcosis employing recombinant EmP29 antigen. PLoS Negl Trop Dis 9(6):e0003795

    Article  Google Scholar 

  • Cai D-M, Wang H-Y, Wang X-L, Jiang Y, Luo Y, Li Y-Z (2017) Ultrasonographic findings of small lesion of hepatic alveolar echinococcosis. Acta Trop 174:165–170

    Article  Google Scholar 

  • Dang Z, Feng J, Yagi K, Sugimoto C, Li W, Oku Y (2012a) Mucosal adjuvanticity of Fibronectin-Binding Peptide (FBP) fused with Echinococcus multilocularis tetraspanin 3: systemic and local antibody responses. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0001842

    Article  PubMed  PubMed Central  Google Scholar 

  • Dang Z, Yagi K, Oku Y, Kouguchi H, Kajino K, Matsumoto J, Nakao R, Wakaguri H, Toyoda A, Yin H (2012b) A pilot study on developing mucosal vaccine against alveolar echinococcosis (AE) using recombinant tetraspanin 3: vaccine efficacy and immunology. PLoS Negl Trop Dis 6(3):e1570

    Article  CAS  Google Scholar 

  • Eckert J, Deplazes P (2004) Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev 17(1):107–135

    Article  Google Scholar 

  • Guo L, Liu K, Xu G, Li X, Tu J, Tang F, Xing Y, Xi T (2012) Prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA against Helicobacter pylori infection in a BALB/c mice model. Appl Microbiol Biotechnol 95(6):1437–1444

    Article  CAS  Google Scholar 

  • Guo L, Yin R, Liu K, Lv X, Li Y, Duan X, Chu Y, Xi T, Xing Y (2014) Immunological features and efficacy of a multi-epitope vaccine CTB-UE against i in BALB/c mice model. Appl Microbiol Biotechnol 98(8):3495–3507

    Article  CAS  Google Scholar 

  • Jazouli M, Lightowlers MW, Bamouh Z, Gauci CG, Tadlaoui K, Ennaji MM, Elharrak M (2020) Immunological responses and potency of the EG95NC(-) recombinant sheep vaccine against cystic echinococcosis. Parasitol Int 78:102149

    Article  CAS  Google Scholar 

  • Kovacs-Nolan J, Latimer L, Landi A, Jenssen H, Hancock R, Babiuk L (2009) The novel adjuvant combination of CpG ODN, indolicidin and polyphosphazene induces potent antibody-and cell-mediated immune responses in mice. Vaccine 27(14):2055–2064

    Article  CAS  Google Scholar 

  • Li R, Yang Q, Guo L, Feng L, Wang W, Liu K, Tang F, Ge R-L (2018) Immunological features and efficacy of the recombinant subunit vaccine LTB-EMY162 against Echinococcus multilocularis metacestode. Appl Microbiol Biotechnol 102(5):2143–2154

    Article  CAS  Google Scholar 

  • Lublin A, Katz C, Gruzdev N, Yadid I, Bloch I, Farnoushi Y, Simanov L, Berkowitz A, Elyahu D, Pitcovski J, Shahar E (2022) Protection against avian coronavirus conferred by oral vaccination with live bacteria secreting LTB-fused viral proteins. Vaccine 40(5):726–733

    Article  CAS  Google Scholar 

  • Ma X, Wang L, Zhao H, Pang N, Zhang F, Jiang T, Liu X, Mamuti W, Wen H, Ding J (2014) Th17 cells are associated with the Th1/Th2-cell balance during Echinococcus multilocularis infection. Mol Med Rep 10(1):236–240

    Article  CAS  Google Scholar 

  • Meinel TR, Gottstein B, Geib V, Keel MJ, Biral R, Mohaupt M, Brügger J (2018) Vertebral alveolar echinococcosis—a case report, systematic analysis, and review of the literature. Lancet Infect Dis 18(3):e87–e98

    Article  Google Scholar 

  • Pang C, Chu YK (2015) Recurrence of liver transplantation combined with lung and diaphragm resection for alveolar echinococcosis: a case report. Transplant Proc 47(7):2278–2281

    Article  CAS  Google Scholar 

  • Pang M-Q, Tang F, Wang H-J, Zhou Y, Ren L, Li R-L, Zhou H, Wan C-F, Liu C-C, Yangdan C-R (2020) Prediction and identification of epitopes in the Emy162 antigen of Echinococcus multilocularis. Acta Parasitol 65(4):919–928

    Article  Google Scholar 

  • Pang MQ, Lu YQ, Tang F, Wang HJ, Zhou Y, Ren L, Li RL, Zhou H, Wan CF, Liu CC, Luosang D, Yangdan C, Fan HN (2022) Prediction and identification of epitopes in the Echinococcus multilocularis thrombospondin 3 antigen. Technol Health Care. https://doi.org/10.3233/THC-212983

    Article  PubMed  Google Scholar 

  • Sagara I, Ellis RD, Dicko A, Niambele MB, Kamate B, Guindo O, Sissoko MS, Fay MP, Guindo MA, Kante O (2009) A randomized and controlled Phase 1 study of the safety and immunogenicity of the AMA1-C1/Alhydrogel®+ CPG 7909 vaccine for Plasmodium falciparum malaria in semi-immune Malian adults. Vaccine 27(52):7292–7298

    Article  CAS  Google Scholar 

  • Tengvall S, Josefsson A, Holmgren J, Harandi AM (2005) CpG oligodeoxynucleotide augments HSV-2 glycoprotein D DNA vaccine efficacy to generate T helper 1 response and subsequent protection against primary genital herpes infection in mice. J Reprod Immunol 68(1–2):53–69

    Article  CAS  Google Scholar 

  • Wang J, Gottstein B (2016) Immunoregulation in larval Echinococcus multilocularis infection. Parasite Immunol 38(3):182–192

    Article  CAS  Google Scholar 

  • Wang L, Wei W, Zhou P, Liu H, Yang B, Feng L, Ge RL, Li R, Tang F (2021) Enzymatic characteristics and preventive effect of leucine aminopeptidase against Echinococcus multilocularis. Acta Trop 222:106066

    Article  CAS  Google Scholar 

  • Yang X, Kang Y, Qiao Y, Li W, Cao J, Li H, Bao H (2019) Magnetic resonance imaging evaluation of characteristics of vascular invasion in intermediate and advanced hepatic alveolar echinococcosis. Exp Ther Med 17(5):4197–4204

    PubMed  PubMed Central  Google Scholar 

  • Zerna G, Rathinasamy VA, Toet H, Anderson G, Dempster R, Spithill TW, Beddoe T (2021) Evaluation of immunogenicity and efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) fused to E. coli heat-labile enterotoxin B subunit LTB adjuvant following intranasal vaccination of cattle. Vaccines 9(11):1213

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the staff at the Altitude Research Center for all the technical support.

Funding

This work was funded by the Province Natural Science Foundation of Qinghai (No. 2017-ZJ-703, Feng Tang), National Natural Science Foundation of China (No.81860299, Tang F), the “Thousand Talents Program” for High-end Innovation of Qinghai Province (Li RL, Tang F), Ningxia Key Research and Development Project (2020BFG02012), and the Qinghai University Undergraduate Innovation and Entrepreneurship Training Project (2019-QH-03).

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Authors

Contributions

Feng Tang, Le Guo, Haining Fan and Ri-li Ge conceived and designed research. Runle Li, Kunmei Liu, Lin Feng and Binwen Hu conducted experiments. Jinwei Ma, Mingyuan Xin, Mingquan Pang, Pei Zhou contributed analytical tools and analyzed data. Runle Li wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Le Guo or Feng Tang.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature that could be construed as influencing the position presented in the manuscript.

Ethical Approval

All animal procedures were approved by were approved by the Animal Ethical and Experimental Committee of Qinghai University (QHDX-2019-09).

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Li, R., Xin, M., Liu, K. et al. Production and Evaluation of a Novel Multi-Epitope Bivalent Vaccine Against Echinococcus multilocaularis Metacestode. Int J Pept Res Ther 28, 114 (2022). https://doi.org/10.1007/s10989-022-10421-1

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