Skip to main content

Helminth parasite proteomics: from experimental models to human infections


Schistosomiasis is a major human helminth infection endemic in developing countries. Urogenital schistosomiasis, caused by S. haematobium, is the most prevalent human schistosome disease in sub-Saharan Africa. Currently control of schistosome infection is by treatment of infected people with the anthelmintic drug praziquantel, but there are calls for continued efforts to develop a vaccine against the parasites. In order for successful vaccine development, it is necessary to understand the biology and molecular characteristics of the parasite. Ultimately, there is need to understand the nature and dynamics of the relationship between the parasite and the natural host. Thus, my studies have focused on molecular characterization of different parasite stages and integrating this information with quantitative approaches to investigate the nature and development of protective immunity against schistosomes in humans. Proteomics has proved a powerful tool in these studies allowing the proteins expressed by the parasite to be characterized at a molecular and immunological level. In this review, the application of proteomic approaches to understanding the human-schistosome relationship as well as testing specific hypotheses on the nature and development of schistosome-specific immune responses is discussed. The contribution of these approaches to informing schistosome vaccine development is highlighted.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Helminth parasite proteomics: from experimental models to human infections
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Helminth parasite proteomics: from experimental models to human infections
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Helminth parasite proteomics: from experimental models to human infections
      Available formats
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
*Corresponding Author: Dr Francisca Mutapi, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Rd, Edinburgh, EH9 3JT. Tel: +44 131 650 8662. Fax: +44 131 650 5450. E-mail:
Hide All
Alban, A., David, S. O., Bjorkesten, L., Andersson, C., Sloge, E., Lewis, S. and Currie, I. (2003). A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 3, 3644.
Allen, J. E. and Maizels, R. M. (2011). Diversity and dialogue in immunity to helminths. Nature Reviews Immunology 11, 375388.
Anderson, R. M. and May, R. M. (1992). Infectious Diseases of Humans: Dynamics and Control. Oxford Science.
Andrews, P. (1985). Praziquantel: mechanisms of anti-schistosomal activity. Pharmacological Therapy 29, 129156.
Berriman, M., Haas, B. J., LoVerde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., DeMarco, R., Djikeng, A., Eyre, T., Gamble, J. A., Ghedin, E., Gu, Y., Hertz-Fowler, C., Hirai, H., Hirai, Y., Houston, R., Ivens, A., Johnston, D. A., Lacerda, D., Macedo, C. D., McVeigh, P., Ning, Z., Oliveira, G., Overington, J. P., Parkhill, J., Pertea, M., Pierce, R. J., Protasio, A. V., Quail, M. A., Rajandream, M. A., Rogers, J., Sajid, M., Salzberg, S. L., Stanke, M., Tivey, A. R., White, O., Williams, D. L., Wortman, J., Wu, W., Zamanian, M., Zerlotini, A., Fraser-Liggett, C. M., Barrell, B. G. and El-Sayed, N. M. (2009). The genome of the blood fluke Schistosoma mansoni. Nature 460, 352358.
Bethony, J. M., Cole, R. N., Guo, X., Kamhawi, S., Lightowlers, M. W., Loukas, A., Petri, W., Reed, S., Valenzuela, J. G. and Hotez, P. J. (2011). Vaccines to combat the neglected tropical diseases. Immunology Reviews 239, 237270.
Black, C. L., Muok, E. M., Mwinzi, P. N., Carter, J. M., Karanja, D. M., Secor, W. E. and Colley, D. G. (2010 a). Increases in levels of schistosome-specific immunoglobulin E and CD23(+) B cells in a cohort of kenyan children undergoing repeated treatment and reinfection with Schistosoma mansoni. Journal of Infectious Diseases 202, 399405.
Black, C. L., Mwinzi, P. N., Muok, E. M., Abudho, B., Fitzsimmons, C. M., Dunne, D. W., Karanja, D. M., Secor, W. E. and Colley, D. G. (2010 b). Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni. PLoS Neglected Tropical Dieases 4, e637.
Bourke, C. D., Maizels, R. M. and Mutapi, F. (2011). Acquired immune heterogeneity and its sources in human helminth infection. Parasitology 138, 139159.
Bowles, J., Hope, M., Tiu, W. U., Liu, X. and McManus, D. P. (1993). Nuclear and mitochondrial genetic markers highly conserved between Chinese and Philippine Schistosoma japonicum. Acta Tropica 55, 217229.
Cook, P. C., Aynsley, S. A., Turner, J. D., Jenkins, G. R., Van Rooijen, N., Leeto, M., Brombacher, F. and Mountford, A. P. (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. PLoS Pathogens 7, e1001323.
Correa-Oliveira, R., Dusse, L. M., Viana, I. R., Colley, D. G., Santos Carvalho, O. and Gazzinelli, G. (1988). Human antibody responses against schistosomal antigens. I. Antibodies from patients with Ancylostoma, Ascaris lumbricoides or Schistosoma mansoni infections react with schistosome antigens. American Journal of Tropical Medicine and Hygiene 38, 348355.
Curwen, R. S., Ashton, P. D., Johnston, D. A. and Wilson, R. A. (2004). The Schistosoma mansoni soluble proteome: a comparison across four life-cycle stages. Molecular and Biochemical Parasitology 138, 5766.
DeMarco, R., Mathieson, W., Manuel, S. J., Dillon, G. P., Curwen, R. S., Ashton, P. D., Ivens, A. C., Berriman, M., Verjovski-Almeida, S. and Wilson, R. A. (2010). Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts. Genome Research 20, 11121121.
Driguez, P., Doolan, D. L., Loukas, A., Felgner, P. L. and McManus, D. P. (2010). Schistosomiasis vaccine discovery using immunomics. Parasites and Vectors 3, 4.
Dunne, D. W., Butterworth, A. E., Fulford, A. J., Ouma, J. H. and Sturrock, R. F. (1992). Human IgE responses to Schistosoma mansoni and resistance to reinfection. Memorias do Instistuto de Oswaldo Cruz 87 (Suppl. IV), 99103.
Dupre, L., Herve, M., Schacht, A. M., Capron, A. and Riveau, G. (1999). Control of schistosomiasis pathology by combination of Sm28GST DNA immunization and praziquantel treatment. Journal of Infectious Diseases 180, 454463.
Fallon, P. G., Smith, P., Nicholls, T., Modha, J. and Doenhoff, M. J. (1994). Praziquantel induced exposure of Schistosoma mansoni alkaline phosphatase: drug-antibody synergy which acts preferentially against female worms. Parasite Immunology 16, 529535.
Fulford, A. C. J., Butterworth, A. E., Ouma, H. J. and Sturrock, R. F. (1995). A statistical approach to schistosome population dynamics and estimation of the life- span of Schistosoma mansoni in man. Parasitology 110, 307316.
Grogan, J., Rotmans, P., Ghoneim, H., Deelder, A., Yazdanbakhsh, M. and Klinkert, M. Q. (1997). Recognition of Schistosoma mansoni cathepsins B and L by human IgG1 and IgG4 antibodies. Parasite Immunology 19, 215220.
Grzych, J. M., Grezel, D., Xu, C. B., Neyrinck, J. L., Capron, M., Ouma, J. H., Butterworth, A. E. and Capron, A. (1993). IgA antibodies to a protective antigen in human Schistosomiasis mansoni. Journal of Immunology 150, 527535.
Hagan, P. (1992). IgE and protective Immunity. Parasite Immunology 15, 14.
Hagan, P., Blumenthal, U. J., Dunne, D., Simpson, A. J. G. and Wilkins, A. H. (1991). Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349, 234245.
Hagel, I., Lynch, N. R., Puccio, F., Rodriguez, O., Luzondo, R., Rodriguez, P., Sanchez, P., Cabrera, C. M. and Di Prisco, M. C. (2003). Defective regulation of the protective IgE response against intestinal helminth Ascaris lumbricoides in malnourished children. Journal of Tropical Pediatrics 49, 136142.
Higon, M., Monteagudo, C., Fried, B., Esteban, J. G., Toledo, R. and Marcilla, A. (2008). Molecular cloning and characterization of Echinostoma caproni heat shock protein-70 and differential expression in the parasite derived from low- and high-compatible hosts. Parasitology 135, 14691477.
Huyse, T., Webster, B. L., Geldof, S., Stothard, J. R., Diaw, O. T., Polman, K. and Rollinson, D. (2009). Bidirectional introgressive hybridization between a cattle and human schistosome species. PLoS Pathogens 5, e1000571.
Kaufmann, S. H. (1990 a). Heat-shock proteins: a missing link in the host-parasite relationship? Medical Microbiology and Immunology 179, 6166.
Kaufmann, S. H. (1990 b). Heat shock proteins and the immune response. Immunology Today 11, 129136.
Kjetland, E. F., Ndhlovu, P. D., Gomo, E., Mduluza, T., Midzi, N., Gwanzura, L., Mason, P. R., Sandvik, L., Friis, H. and Gundersen, S. G. (2006). Association between genital schistosomiasis and HIV in rural Zimbabwean women. Aids 20, 593600.
Kwan-Lim, G. E., Forsyth, K. P. and Maizels, R. M. (1990). Filarial-specific IgG4 response correlates with active Wuchereria bancrofti infection. Journal of Immunology 145, 42984305.
Lightowlers, M. W., Colebrook, A. L., Gauci, C. G., Gauci, S. M., Kyngdon, C. T., Monkhouse, J. L., Vallejo Rodriquez, C., Read, A. J., Rolfe, R. A. and Sato, C. (2003). Vaccination against cestode parasites: anti-helminth vaccines that work and why. Veterinary Parasitology 115, 83123.
Liu, S. X., Song, G. C., Xu, Y. X., Yang, W. and McManus, D. P. (1995). Anti-fecundity immunity induced in pigs vaccinated with recombinant Schistosoma japonicum 26 kDa glutathione-S-transferase. Parasite Immunology 17, 355–340.
Lopez, J. L. (2007). Two-dimensional electrophoresis in proteome expression analysis. Journal of Chromatography B 849, 190202.
Machado-Silva, J. R., Neves, H. R., Rodrigues-Silva, R., Figueiredo de Oliveira, R. M. and Maldonado, A. (2011). Assessment of Akodon cursor (Rodentia, Sigmodontinae) as permissive host to Schistosoma mansoni infection: morphology of adult worms. Acta Parasitologica 56, 147153.
Maizels, R. M. and Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology 3, 733744.
Maresca, B. and Kobayashi, G. S. (1994). Hsp70 in parasites: as an inducible protective protein and as an antigen. Experientia 50, 10671074.
Mathieson, W., Castro-Borges, W. and Wilson, R. A. (2011). The proteasome-ubiquitin pathway in the Schistosoma mansoni egg has development- and morphology-specific characteristics. Molecular and Biochemical Parasitology 175, 118125.
Mathieson, W. and Wilson, R. A. (2010). A comparative proteomic study of the undeveloped and developed Schistosoma mansoni egg and its contents: the miracidium, hatch fluid and secretions. International Journal for Parasitology 40, 617628.
McManus, D. P. and Loukas, A. (2008). Current status of vaccines for schistosomiasis. Clinical Microbiology Reviews 21, 225242.
Meeusen, E. N., Walker, J., Peters, A., Pastoret, P. P. and Jungersen, G. (2007). Current status of veterinary vaccines. Clinical Microbiology Reviews 20, 489510, table of contents.
Mitchell, K. M., Mutapi, F. and Woolhouse, M. E. (2008). The predicted impact of immunosuppression upon population age-intensity profiles for schistosomiasis. Parasite Immunology 9, 462470.
Mutapi, F., Bourke, C., Harcus, Y., Midzi, N., Mduluza, T., Turner, C. M., Burchmore, R. and Maizels, R. M. (2011). Differential recognition patterns of Schistosoma haematobium adult worm antigens by the human antibodies IgA, IgE, IgG1 and IgG4. Parasite Immunology 33, 181192.
Mutapi, F., Burchmore, R., Mduluza, T., Foucher, A., Harcus, Y., Nicoll, G., Midzi, N., Turner, C. M. and Maizels, R. M. (2005). Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances serological recognition of defined parasite antigens. Journal of Infectious Diseases 192, 11081118.
Mutapi, F., Burchmore, R., Mduluza, T., Midzi, N., Turner, C. M. and Maizels, R. M. (2008). Age-related and infection intensity-related shifts in antibody recognition of defined protein antigens in a schistosome-exposed population. Journal of Infectious Diseases 198, 167175.
Parkin, D. M. (2008). The global burden of urinary bladder cancer. Scandinavian Journal of Urology and Nephrology Supplement 118, 1220.
Quinnell, R. J., Woolhouse, M. E. J., Walsh, E. A. and Pritchard, D. J. (1995). Immunoepidemiology of human necatorisis: correlations between antibody responses and parasite burdens. Parasite Immunology 17, 313318.
Roestenberg, M., McCall, M., Hopman, J., Wiersma, J., Luty, A. J., van Gemert, G. J., van de Vegte-Bolmer, M., van Schaijk, B., Teelen, K., Arens, T., Spaarman, L., de Mast, Q., Roeffen, W., Snounou, G., Renia, L., van der Ven, A., Hermsen, C. C. and Sauerwein, R. (2009). Protection against a malaria challenge by sporozoite inoculation. New England Journal of Medicine 361, 468477.
Rollinson, D., Kaukas, A., Johnston, D. A., Simpson, A. J. G. and Tanaka, M. (1997). Some molecular insights into schistosome evolution. International Journal for Parasitology 27, 1128.
Sirag, S. B., Christensen, N. O., Frandsen, F., Monrad, J. and Nansen, P. (1980). Homologous and heterologous resistance in Echinostoma revolutum infections in mice. Parasitology 80, 479486.
Smith, R. E., Spithill, T. W., Pike, R. N., Meeusen, E. N. and Piedrafita, D. (2008). Fasciola hepatica and Fasciola gigantica:cloning and characterisation of 70 kDa heat-shock proteins reveals variation in HSP70 gene expression between parasite species recovered from sheep. Experimental Parasitology 118, 536542.
Tyers, M. and Mann, M. (2003). From genomics to proteomics. Nature 422, 193197.
Webster, B. L., Southgate, V. R., Timothy, D. and Littlewood, J. (2006). A revision of the interrelationships of Schistosoma including the recently described Schistosoma guineensis. International Journal for Parasitology 36, 947955.
Wherry, E. J., Teichgraber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., von Andrian, U. H. and Ahmed, R. (2003). Lineage relationship and protective immunity of memory CD8 T cell subsets. Nature Immunology 4, 225234.
Wilson, M. S., Cheever, A. W., White, S. D., Thompson, R. W. and Wynn, T. A. (2011). IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. PLoS Pathogens 7, e1002171.
Woolhouse, M. E. (1998). Patterns in parasite epidemiology: the peak shift. Parasitology Today 14, 428434.
Woolhouse, M. E. and Hagan, P. (1999). Seeking the ghost of worms past. Nature Medicine 5, 12251227.
World Health Organisation (2011). First WHO report on neglected tropical diseases 2010: working to overcome the global impact of neglected tropical diseases. WHO, Geneva.
Yazdanbakhsh, M. and Sacks, D. L. (2010). Why does immunity to parasites take so long to develop? Nature Reviews Immunology 10, 8081.
Yildiz, B. and Kural, N. (2007). IgG1 deficiency and high IgA level with juvenile idiopathic arthritis. European Journal of Pediatrics 166, 11791180.
Zhou, Y., Zheng, Z., Chen, Y., Zhang, L., Wang, K., Guo, J., Huang, Z. and Zhang, B. (2009). The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460, 345351.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 6
Total number of PDF views: 85 *
Loading metrics...

Abstract views

Total abstract views: 217 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th March 2018. This data will be updated every 24 hours.