Hostname: page-component-77c89778f8-rkxrd Total loading time: 0 Render date: 2024-07-18T12:38:27.812Z Has data issue: false hasContentIssue false
  • English
  • Français

Schistosoma mansoni cercarial elastase (SmCE): differences in immunogenic properties of native and recombinant forms

Published online by Cambridge University Press:  08 May 2017

MARWA H. EL-FAHAM Open the ORCID record for MARWA H. EL-FAHAM [Opens in a new window] ,
KATHERINE J. WHEATCROFT-FRANCKLOW ,
HELEN P. PRICE ,
JON R. SAYERS  and
MICHAEL J. DOENHOFF
MARWA H. EL-FAHAM*
Affiliation:
School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
KATHERINE J. WHEATCROFT-FRANCKLOW
Affiliation:
School of Biological Sciences, Bangor University, Bangor, Gwynedd LL57 2UW, UK
HELEN P. PRICE
Affiliation:
Faculty of Natural Sciences, School of Life Sciences, Keele University, Newcastle-under-Lyme ST5 5BG, UK
JON R. SAYERS
Affiliation:
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK
MICHAEL J. DOENHOFF
Affiliation:
School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
*
*Corresponding author: Medical Parasitology Department, Faculty of Medicine, Alexandria University, Egypt. E-mail: marwaelfaham@yahoo.com
Get access Rights & Permissions [Opens in a new window]

Summary

The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude preparations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum glutathione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization. The IgG antibody response to rSmCE-SjGST was mainly of the IgG1 subclass. These results suggest that inactive forms of the antigen could be used to obtain the optimum immunogenic effects as a vaccine candidate against schistosomiasis. Mice immunized with the rSmCE-SjGST on alum had smaller mean worm burdens and lower tissue egg counts when compared with adjuvant alone- and recombinant SjGST-injected controls. The native SmCE was antigenically cross-reactive with homologous enzymes of Schistosoma haematobium and Schistosoma margrebowiei.

Keywords

cercarial elastaseSchistosoma mansonienzymeimmunogenicityvaccineantigenrecombinantGST fusion protein
Type
Research Article
Information
Parasitology , Volume 144 , Issue 10 , September 2017 , pp. 1356 - 1364
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

These authors contributed equally to this paper.

References

Auriault, C., Ouaissi, M. A., Torpier, G., Eisen, H. and Capron, A. (1981). Proteolytic cleavage of IgG bound to the Fc receptor of Schistosoma mansoni schistosomula. Parasite Immunology 3, 33–44.Google Scholar
Bahgat, M. K. F., Doenhoff, M. J., Li, Y., Ramzy, R. M., Kirsten, C. and Ruppel, A. (2001). Infection induces antibodies against the cercarial secretions, but not against the cercarial elastases of Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum and Trichobilharzia ocellata . Parasite Immunology 23, 557–565.Google Scholar
Bergquist, N. R. and Colley, D. G. (1998). Schistosomiasis vaccines: research to development. Parasitology Today 14, 99–104.CrossRefGoogle ScholarPubMed
Bethony, J. M., Simon, G., Diemert, D. J., Parenti, D., Desrosiers, A., Schuck, S., Fujiwara, R., Santiago, H. and Hotez, P. J. (2008). Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults. Vaccine 26, 2408–2419.Google Scholar
Cohen, F. E., Gregoret, L. M., Amiri, P., Aldape, K., Railey, J. and Mckerrow, J. H. (1991). Arresting tissue invasion of a parasite by protease inhibitors chosen with the aid of computer modeling. Biochemistry 30, 11221–11229.Google Scholar
Colley, D. G. and Wikel, S. K. (1974). Schistosoma mansoni: simplified method for the production of schistosomules. Experimental Parasitology 35, 44–51.Google Scholar
Darani, H. Y. (1997). Immunology of schistosome proteases. Ph.D. thesis, University of Wales.Google Scholar
Darani, H. Y., Curtis, R. H. C., McNeice, C., Price, H. P., Sayers, J. R. and Doenhoff, M. J. (1997). Schistosoma mansoni: anomalous immunogenic properties of a 27 kDa larval serine protease associated with protective immunity. Parasitology 115, 237–247.Google Scholar
Davern, K. M., Tiu, W. U., Morahan, G., Wright, M. D., Garcia, E. G. and Mitchell, G. F. (1987). Responses in mice to Sj26, a glutathione S-transferase of Schistosoma japonicum worms. Immunology and Cell Biology 65, 473–482.CrossRefGoogle ScholarPubMed
Doenhoff, M. J. (1998). A vaccine for schistosomiasis: alternative approaches. Parasitology Today 14, 105–109.Google Scholar
Doenhoff, M., Bickle, Q., Long, E., Bain, J. and McGregor, A. (1978 a). Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. I. Demonstration of resistance to reinfection using a model system that involves perfusion of mice within three weeks of challenge. Journal of Helminthology 52, 173–186.CrossRefGoogle Scholar
Doenhoff, M., Musallam, R., Bain, J. and Mcgregor, A. (1978 b). Studies on the host-parasite relationship in Schistosoma mansoni-infected mice: the immunological dependence of parasite egg excretion. Immunology 35, 771–778.Google Scholar
Fitzpatrick, J. M., Peak, E., Perally, S., Chalmers, I. W., Barrett, J., Yoshino, T. P., Ivens, A. C. and Hoffmann, K. F. (2009). Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses. PLoS Neglected Tropical Diseases 3, e543.CrossRefGoogle ScholarPubMed
Ghendler, Y., Parizade, M., Arnon, R., Mckerrow, J. H. and Fishelson, Z. (1996). Schistosoma mansoni: evidence for a 28-kDa membrane-anchored protease on schistosomula. Experimental Parasitology 83, 73–82.Google Scholar
Guan, K. L. and Dixon, J. E. (1991). Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Analytical Biochemistry 192, 262–267.Google Scholar
Henkle, K. J., Davern, K. M., Wright, M. D., Ramos, A. J. and Mitchell, G. F. (1990). Comparison of the cloned genes of the 26- and 28-kilodalton glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni . Molecular and Biochemical Parasitology 40, 23–34.CrossRefGoogle ScholarPubMed
Hotez, P. J., Alvarado, M., Basanez, M. G., Bolliger, I., Bourne, R., Boussinesq, M., et al. (2014). The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Neglected Tropical Diseases 8, e2865.Google Scholar
Knudsen, G. M., Medzihradszky, K. F., Lim, K. C., Hansell, E. and McKerrow, J. H. (2005). Proteomic analysis of Schistosoma mansoni cercarial secretions. Molecular and Cellular Proteomics 4, 1862–1875.Google Scholar
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.Google Scholar
Marikovsky, M., Arnon, R. and Fishelson, Z. (1988). Proteases secreted by transforming schistosomula of Schistosoma mansoni promote resistance to killing by complement. The Journal of Immunology 141, 273–278.CrossRefGoogle ScholarPubMed
Marikovsky, M., Arnon, R. and Fishelson, Z. (1990 a). Schistosoma-mansoni – localization of the 28kda secreted protease in cercaria. Parasite Immunology 12, 389–401.Google Scholar
Marikovsky, M., Parizade, M., Arnon, R. and Fishelson, Z. (1990 b). Complement regulation on the surface of cultured schistosomula and adult worms of Schistosoma-mansoni . European Journal of Immunology 20, 221–227.Google Scholar
Mast, A. E., Enghild, J. J., Pizzo, S. V. and Salvesen, G. (1991). Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive site cleaved serpins: comparison of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-antiplasmin, angiotensinogen, and ovalbumin. Biochemistry 30, 1723–1730.CrossRefGoogle ScholarPubMed
Modha, J. and Doenhoff, M. J. (1994 a). Complex formation of human alpha-1-antitrypsin with components in Schistosoma mansoni cercariae. Parasite Immunology 16, 447–450.Google Scholar
Modha, J. and Doenhoff, M. J. (1994 b). Schistosoma mansoni host-parasite relationship: interaction of contrapsin with adult worms. Parasitology 109, 487–495.CrossRefGoogle ScholarPubMed
Molehin, A. J., Rojo, J. U., Siddiqui, S. Z., Gray, S. A., Carter, D. and Siddiqui, A. A. (2016). Development of a schistosomiasis vaccine. Expert Review of Vaccines 15, 619–627.CrossRefGoogle ScholarPubMed
Mountford, A. P., Fisher, A. and Wilson, R. A. (1994). The profile of IgG1 and IgG2a antibody responses in mice exposed to Schistosoma mansoni . Parasite Immunology 16, 521–527.CrossRefGoogle ScholarPubMed
Pleass, R. J., Kusel, J. R. and Woof, J. M. (2000). Cleavage of human IgE mediated by Schistosoma mansoni . International Archives of Allergy and Immunology 121, 194–204.CrossRefGoogle ScholarPubMed
Price, H. P., Doenhoff, M. J. and Sayers, J. R. (1997). Cloning, heterologous expression and antigenicity of a schistosome cercarial protease. Parasitology 114, 447–453.Google Scholar
Salter, J. P., Choe, Y., Albrecht, H., Franklin, C., Lim, K. C., Craik, C. S. and McKerrow, J. H. (2002). Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. The Journal of Biological Chemistry 277, 24618–24624.CrossRefGoogle ScholarPubMed
Sambrook, J., Fritsch, E. F. and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd Edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, USA.Google Scholar
Schechtman, D., Tarrab-Hazdai, R. and Arnon, R. (2001). The 14–3–3 protein as a vaccine candidate against schistosomiasis. Parasite Immunology 23, 213–217.Google Scholar
Scott, J. C. and McManus, D. P. (2000). 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 49, 289–300.CrossRefGoogle ScholarPubMed
Sher, A. (1988). Strategies for vaccination against parasites. In The Biology of Parasitism (ed. Englund, P. T. and Sher, A.), pp. 169–172. Alan R Liss Inc, New York, USA.Google Scholar
Simons, P. C. and Vander Jagt, D. L. (1981). Purification of glutathione S-transferase by glutathione-affinity chromatography. Methods in Enzymology 77, 235–237.Google Scholar
Smith, D. B., Davern, K. M., Board, P. G., Tiu, W. U., Garcia, E. G. and Mitchell, G. F. (1986). Mr 26 000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase. Proceedings of the National Academy of Sciences of the United States of America 83, 8703–8707.Google Scholar
Smith, H., Doenhoff, M., Aitken, C., Bailey, W., Ji, M. and Dawson, E. (2012). Comparison of Schistosoma mansoni soluble cercarial antigens and soluble egg antigens for serodiagnosing Schistosome infections. PLoS Neglected Tropical Diseases 6, e1815.Google Scholar
Smithers, S. R. and Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 55, 695–700.Google Scholar
Tiu, W. U., Davern, K. M., Wright, M. D., Board, P. G. and Mitchell, G. F. (1988). Molecular and serological characteristics of the glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni . Parasite Immunology 10, 693–706.Google Scholar
Towbin, H., Staehlin, T. and Gordon, J. M. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences of the United States of America 76, 4350–4354.CrossRefGoogle ScholarPubMed
Voller, A., Bidwell, D. E. and Bartlett, A. (1976). Enzyme immunoassays in diagnostic medicine. Theory and practice. Bulletin of the World Health Organization 53, 55–65.Google Scholar