Skip to main content

Advertisement

SpringerLink
Log in

Immunization with recombinant schistosome adenylate kinase 1 partially protects mice against Schistosoma japonicum infection

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Highly effective and safe prophylactic vaccines are urgently needed to sustainably control schistosomiasis, one of the most serious endemic zoonoses in China. In this study, we characterized adenylate kinase 1 from Schistosoma japonicum (SjAK1), a phosphotransferase that regulates cellular energy and metabolism, and evaluated its potential as a recombinant vaccine. Based on real-time quantitative PCR, western blot, and immunolocalization, SjAK1 is active throughout the life of the worm, although its expression is higher in 21-day-old schistosomula, adult worms, and eggs deposited in the host liver. Further, the enzyme accumulates in the eggshell, intestinal epithelium, integument of adult worms and in the vitellaria tissue in female worms. A 594-bp full-length complementary DNA (cDNA) encoding SjAK1 was synthesized from total RNA of 3-day-old schistosomes, and immunization with recombinant SjAK1 reduced worm burden by 50%, decreased the density of eggs deposited in the host liver by 40%, and reduced the area of granulomas in the host liver by 56%. ELISA results showed that recombinant SjAK1 also stimulated Th1 cytokines such as IL-2 and IFN-γ, but not IL-5 and IL-4. Collectively, a recombinant form of the enzyme SjAK1 elicits partial protective immunity against Schistosoma japonicum infection and the induction of Th1 cytokines. Thus, the enzyme has potential as a component of a multivalent vaccine against schistosomiasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abrusci P, Chiarelli LR, Galizzi A, Fermo E, Bianchi P, Zanella A, Valentini G (2007) Erythrocyte adenylate kinase deficiency: characterization of recombinant mutant forms and relationship withnonspherocytic hemolytic anemia. Exp Hematol 35(8):1182–1189

    Article  CAS  PubMed  Google Scholar 

  • Cardoso FC, Macedo GC, Gava E, Kitten GT, Mati VL, de Melo AL, Caliari MV, Almeida GT, Venancio TM, Verjovski-Almeida S, Oliveira SC (2008) Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection. PLoS Negl Trop Dis 2(10):e308

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen L, Chen Y, Zhang D, Hou M, Yang B, Zhang F, Zhang W, Luo X, Ji M, Wu G (2016) Protection and immunological study on two tetraspanin-derived vaccine candidates against schistosomiasis japonicum. Parasite Immunol 38(10):589–598

    Article  CAS  PubMed  Google Scholar 

  • Cheng G, Fu Z, Lin J, Shi Y, Zhou Y, Jin Y, Cai Y (2009) In vitro and in vivo evaluation of small interference RNA-mediated gynaecophoral canal protein silencing in Schistosoma japonicum [J]. J Gene Med 11(5):412–421

    Article  CAS  PubMed  Google Scholar 

  • Cupit PM, Cunningham C (2015) What is the mechanism of action of praziquantel and how might resistance strike? Future Med Chem 7(6):701–705

    Article  CAS  PubMed  Google Scholar 

  • Dillon GP, Feltwell T, Skelton JP, Ashton PD, Coulson PS, Quail MA, Nikolaidou-Katsaridou N, Wilson RA, Ivens AC (2006) Microarray analysis identifies genes preferentially expressed in the lung schistosomulum of Schistosoma mansoni. Int J Parasitol 36(1):1–8

    Article  CAS  PubMed  Google Scholar 

  • Duan MM, Xu RM, Yuan CX, Li YY, Liu Q, Cheng GF, Lin JJ, Feng XG (2015) SjHSP70, a recombinant Schistosoma japonicum heat shock protein 70, is immunostimulatory and induces protective immunity against cercarial challenge in mice. Parasitol Res 114(9):3415–3429

    Article  PubMed  Google Scholar 

  • Dzeja P, Terzic A (2009) Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing. Int J Mol Sci 10(4):1729–1772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Ridi R, Tallima H, Mahana N, Dalton JP (2010) Innate immunogenicity and in vitro protective potential of Schistosoma mansoni lung schistosomula excretory-secretory candidate vaccine antigens. Microbes Infect 12(10):700–709

    Article  CAS  PubMed  Google Scholar 

  • Figueiredo BC, Ricci ND, de Assis NR, de Morais SB, Fonseca CT, Oliveira SC (2015) Kicking in the guts: Schistosoma mansoni digestive tract proteins are potential candidates for vaccine development. Front Immunol 6:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Gloria-Bottini F, Neri A, Pietropolli A, Bottini E, Magrini A (2013) Ak(1) genetic polymorphism and season of conception. Eur J Obstet Gynecol Reprod Biol 166(2):161–163

    Article  CAS  PubMed  Google Scholar 

  • Hesse M, Modolell M, Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ, Wynn TA (2001) Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol 167(11):6533–6544

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Huang L, Yang J, Cao X, Han Q, Zhang M, Han Y, Fu Z, Zhu C, Lu K, Li X, Lin J (2015) Cloning, expression and enzymatic characterization of 3-phosphoglycerate kinase from Schistosoma japonicum. Exp Parasitol 159:37–45

    Article  CAS  PubMed  Google Scholar 

  • Hotez PJ, Fenwick A, Savioli L, Molyneux DH (2009) Rescuing the bottom billion through control of neglected tropical disease. Lancet 373:1570–1575

    Article  PubMed  Google Scholar 

  • James SL, Glaven J (1989) Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol 143(12):4208–4212

    CAS  PubMed  Google Scholar 

  • Jankovic D, Wynn TA, Kullberg MC, Hieny S, Caspar P, James S et al (1999) Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanism. J Immunol 162:345–351

    CAS  PubMed  Google Scholar 

  • Janssen E, de Groof A, Wijers M, Fransen J, Dzeja PP, Terzic A, Wieringa B (2003) Adenylate kinase 1 deficiency induces molecular and structural adaptations to support muscle energymetabolism. J Biol Chem 278(15):12937–12945

    Article  CAS  PubMed  Google Scholar 

  • Jones MK, Gobert GN, Zhang L, Sunderland P, McManus DP (2004) The cytoskeleton and motor proteins of human schistosomes and their roles in surface maintenance and host-parasite interactions. BioEssays 26(7):752–765

    Article  CAS  PubMed  Google Scholar 

  • Lei ZL, Zhang LJ, Xu ZM, Dang H, Xu J, Lv S, Cao CL, Li SZ, Zhou XN (2015) Endemic status of schistosomiasis in People’s Republic of China in 2014. Chin J Schisto Control 27(6):563–569 [in Chinese]

    Google Scholar 

  • Liang P, Zhang F, Chen W, Hu X, Huang Y, Li S, Ren M, He L, Li R, Li X, Xu J, Wu Z, Lu G, Yu X (2013) Identification and biochemical characterization of adenylate kinase 1 from Clonorchis sinensis. Parasitol Res 112(4):1719–1727

    Article  PubMed  Google Scholar 

  • Liu LY, Yu XB, Luo SH, Fang JM (1997) Quick isolation and purification of Schistosoma japonicum eggs and their total RNA. Chin J Zoonoses 13(2):17–19 [in Chinese]

    Google Scholar 

  • Liu R, Zhao QP, Ye Q, Xiong T, Tang CL, Dong HF, Jiang MS (2013) Cloning and characterization of a bone morphogenetic homologue of Schistosoma japonicum. Exp Parasitol 135(1):64–71

    Article  CAS  PubMed  Google Scholar 

  • Lu Z, Quack T, Hahnel S, Gelmedin V, Pouokam E, Diener M, Hardt M, Michel G, Baal N, Hackstein H, Grevelding CG (2015) Isolation,enrichment and primary characterissation of vitelline cells from Schistosoma mansoni obtained by theorgan isolation method. Int J Parasitol 45(9–10):663–672

    Article  CAS  PubMed  Google Scholar 

  • Merrifield M, Hotez PJ, Beaumier CM, Gillespie P, Strych U, Hayward T, Bottazzi ME (2016) Advancing a vaccine to prevent human schistosomiasis. Vaccine 29

  • Moloney NA, Doenhoff MJ, Webbe G, Hinchcliffe P (1982) Studies on the host-parasite relationship of Schistosoma japonicum in normal and immunosuppressed mice. Parasite Immunol 4(6):431–440

    CAS  PubMed  Google Scholar 

  • Mountford AP, Harrop R (1998) Vaccination against schistosomiasis: the case for lung-stage antigens. Parasitol Today 14(3):109–114

    Article  CAS  PubMed  Google Scholar 

  • Panayiotou C, Solaroli N, Xu Y, Johansson M, Karlsson A (2011) The characterization of human adenylate kinases 7 and 8 demonstrates differences in kinetic parameters and structural organization among the family of adenylate kinase isoenzymes. Biochem J 433(3):527–534

    Article  CAS  PubMed  Google Scholar 

  • Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2(7):499–511

    Article  CAS  PubMed  Google Scholar 

  • Peng HJ, Chen XG, Li H, Wang CM (2004) Expression of adenylate kinase of Schistosoma japonicum and evaluation on the immunoreactivity of the recombinant protein. Zhong guo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 22(1):46–49

    Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu C, Liu S, Hong Y, Fu Z, Wei M, Ai D, Lin J (2012) Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice. Parasit Vectors 5:172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ricciardi A, Visitsunthorn K, Dalton JP, Ndao M (2016) A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis. BMC Infect Dis 16:112

    Article  PubMed  PubMed Central  Google Scholar 

  • Ruppel A, Shi YE, Moloney NA (1990) Schistosoma mansoni and S. japonicum: comparison of levels of ultraviolet irradiation for vaccination of mice with cercariae. Parasitology 1:23–26

    Article  Google Scholar 

  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mio Biol Evol 30(12):2725–2729

    Article  CAS  Google Scholar 

  • van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D (2003) Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop 86:125–139

    Article  PubMed  Google Scholar 

  • Vieira P, Miranda HP, Cerqueira M, Delgado Mde L, Coelho H, Antunes D, Cross JH, da Costa JM (2007) Latent schistosomiasis in Portuguese soldiers. Mil Med 172(2):144–146

    Article  PubMed  Google Scholar 

  • WHO (2016) Schistosomiasis. WHO Media Centre, Fact sheet N° 115. Available: http://www.who.int/mediacentre/factsheets/fs115/en/. Accessed Feb 2016

  • Wilson RA, Coulson PS, Betts C, Dowling MA, Smythies LE (1996) Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology 87:275–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye Q, Zhu JY, Ming ZP, Zhao QP, Grevelding CG, Liu R, Zhong QP, Jiang MS, Dong HF (2012) Studies on the establishment of a co-culture system of lung stage Schistosoma japonicum with host cells. Parasitol Res 111(2):735–748

    Article  PubMed  Google Scholar 

  • You H, Gobert GN, Cai P, Mou R, Nawaratna S, Fang G, Villinger F, McManus DP (2015) Suppression of the insulin receptors in adult Schistosoma japonicum impacts on parasite growth and development: further evidence of vaccine potential. PLoS Negl Trop Dis 9(5):e0003730

    Article  PubMed  PubMed Central  Google Scholar 

  • Zeng LL, Luo DD, Li SL, Liu W, He YW (2003) Expression of IL-2 and TNF-alpha in the liver and the effect of injection of these cytokines on liver fibrosis in mice infected with Schistosoma japonicum. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 21(3):150–153

    PubMed  Google Scholar 

  • Zhang Y, Xia L, Pang WQ, Wang T, Zhang JF (2011) The function of AK and AMP signaling in body energy sensing and balance. Chin Bull Life Sci 23(5):434–439

    CAS  Google Scholar 

  • Zhang Z, Xu H, Gan W, Zeng S, Hu X (2012) Schistosoma japonicum calcium-binding tegumental protein SjTP22.4 immunization confers praziquantel schistosomulumicide and antifecundity effect in mice. Vaccine 30(34):5141–5150

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z, Fu Z, Zhang M, Han Y, Hong Y, Li D, Zhao Z, Shi Y, Li X, Lin J (2012) Protective efficacy evaluation induced by recombinant protein LHD-Sj23-GST of Schistosoma japonicum emulsified with three different adjuvants. Parasite Immunol 34(6):341–344

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Qian Gao and Xiaoxue Ma for the initial contributions to the project. We also thank Prof. Rui Zhou and Feng Li for the assistance and for providing the laboratory facilities. We are grateful to Christoph Grevelding for the advice on article writing.

Author information

Authors and Affiliations

  1. Hubei Province Key Laboratory of Allergy and Immunology, Department of Parasitology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, 430071, China

    Yanru Gao, Xiaoshan Zhou, Huan Wang, Rong Liu, Qinping Zhao, Zhenping Ming & Huifen Dong

  2. Department of Physiology, School of Basic Medicine Sciences, Hubei University of Science and Technology, Xianning, Hubei Province, 437000, China

    Yanru Gao

  3. Renmin Hospital, Wuhan University, Wuhan, Hubei Province, 430000, China

    Qing Ye

Authors
  1. Yanru Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoshan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qinping Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhenping Ming
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Huifen Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huifen Dong.

Ethics declarations

Funding

This work was funded by the National Natural Science Foundation of China (No. 81273010) and by the Scientific Research Subject of the Health and Family Planning Commission of Hubei Province (No. XF2012-18).

Conflict of interest

The authors declare that they have no conflict interest.

Ethical approval

Animal protocols were in strict compliance with the guidelines of the Association for Assessment and Accreditation of Laboratory Animal Care International and were approved by the Institutional Animal Care and Use Committee of Wuhan University (approval no. 2015-0023).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, Y., Zhou, X., Wang, H. et al. Immunization with recombinant schistosome adenylate kinase 1 partially protects mice against Schistosoma japonicum infection. Parasitol Res 116, 1665–1674 (2017). https://doi.org/10.1007/s00436-017-5441-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-017-5441-y

Keywords

Search

Navigation