Schistosomiasis, the second major parasitic disease in the world after malaria, affects 200 million people. Vaccine strategies represent an essential component of the control of this chronic debilitating disease where the deposition of millions of eggs in the tissues is the main cause of pathology. Research developed in our laboratory over the last 20 years has led to the identification of novel effector mechanisms, pointing for the first time to the protective role of Th2 responses and of IgE antibodies now supported by seven studies in human populations. The identification and molecular cloning of a target antigen, a glutathione S-transferase (GST), has made it possible to demonstrate its vaccine potential in several animal species (rodents, cattle, primates) and to establish consistently the capacity of vaccination to reduce female worm fecundity and egg viability through the production of neutralizing antibodies (IgA and IgG). Following promising preclinical studies, clinical trials (phase I and II) have been undertaken using Schistosoma haematobium GST, Sh28GST. High titers of neutralizing antibodies were produced (IgG3 and IgA) together with Th2 cytokines, consistently with the concepts developed from experimental models. With these results we are on the way towards a feasible approach of vaccine development against a major human parasitic disease.

1.
Ovary Z: Passive cutaneous anaphylaxis; in Ackroyd JF (ed): Immunological Methods. Oxford, Blackwell, 1964, p 259.
2.
Ogilvie BM, Smithers SR, Terry RJ: Reagin-like antibodies in experimental infection of Schistosoma mansoni and the passive transfer of resistance. Nature 1966;209:1221.
3.
Johansson SGO, Bennich HH, Berg T: The clinical significance of IgE. Prog Allergy 1971;1:157.
4.
Dessaint JP, Capron M, Bout D Capron A: Quantitative determination of specific IgE antibodies to schistosome antigens and serum IgE levels in patients with schistosomiasis (S. mansoni or S. haematobium). Clin Exp Immunol 1975;20:427–436.
5.
Jarrett EEE, Miller HRP: Production and activities of IgE in helminth infection. Prog Allergy 1982;31:178–233.
6.
Dessaint JP: Anaphylactic antibodies and their significance. Clin Immunol Allergy 1982;2:621–637.
7.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clones. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348–2357.
8.
Pearce EJ, Sher A: Functional dichotomy in the CD4+ T cell response to Schistosoma mansoni. Exp Parasitol 1991;73:110–116.
9.
Capron A, Dessaint JP, Capron M, Ouma A, Butterworth AE: Immunity to schistosomes: Progress toward vaccine. Science 1987;238:1065–1072.
10.
Capron M, Capron A: Immunoglobulin E and effector cells in schistosomiasis. Science 1994;264:1876.
11.
Verwaerde C, Joseph M, Capron M, Pierce RJ, Damonneville M, Velge F, Auriault C, Capron A: Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni. J Immunol 1987;138:4441–4446.
12.
Capron M, Nogueira-Queiroz JA, Papin JP, Capron A: Interactions between eosinophils and antibodies: In vivo protective role against rat schistosomiasis. Cell Immunol 1984;83:60–72.
13.
Hagan P, Blumenthal UJ, Dunne D, Simpson AJ, Wilkins HA: Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 1991;369:243–245.
14.
Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ: Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur J Immunol 1991;21:2679–2686.
15.
Dunne DW, Butterworth AE, Fulford AJ, Kariuki HC, Langley JG, Ouma JH, Capron A, Pierce RJ, Sturrock RF: Immunity after treatment of human schistosomiasis: Association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol 1992;22:1483–1494.
16.
Viana IRC, Correa-Oliveira R, Dos Santos Carvalho O, Massara CL, Colosimo E, Colley DG, Gazzinelli G: Comparison of antibody isotype responses to Schistosoma mansoni antigens by infected and putative resistant individuals living in an endemic area. Parasite Immunol 1995;17:297–304.
17.
Satti MZ, Lind P, Vennervald BJ, Sulaiman SM, Daffalla AA, Ghalib HW: Specific immunoglobulin measurements related to exposure and resistance to Schistosoma mansoni infection in Sudanese canal cleaners. Clin Exp Immunol 1996;106:45–54.
18.
Ndhlovu P, Cadman H, Vennervald BJ, Christensen NO, Chidimu M, Chandiwana SK: Age-related antibody profiles in Schistosoma haematobium infections in a rural community in Zimbabwe. Parasite Immunol 1996;18:181–191.
19.
Dunne DW, Webster M, Smith P, Langley JG, Richardson BA, Fulford AJ, Butterworth AE, Sturrock RF, Kariuki HC, Ouma JH: The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection. Parasite Immunol 1997;19:79–89.
20.
Zhang Z, Wu H, Chen S, Hu L, Xie Z, Qiu Y, Su C, Cao Y, Wu Y, Zhang S, Wu G: Association between IgE antibody against soluble egg antigen and resistance to reinfection with Schistosoma japonicum. Trans R Soc Trop Med Hyg 1997;91:606–608.
21.
Pearce EJ, Sher A: Functional dichotomy in the CD4+ T cell response to Schistosoma mansoni. Exp Parasitol 1991;73:110–116.
22.
Capron A, Dombrowicz D, Capron M: Regulation of the immune response in experimental and human schistosomiasis: The limits of an attractive paradigm. Microb Infect 1999;1:485.
23.
Grangette C, Gruart V, Ouaissi MA, Rizvi F, Delespesse G, Capron A, Capron M: IgE receptor on human eosinophils (FcεRII): Comparison with B cell CD23 and association with an adhesion molecule. J Immunol 1989;143:3580–3588.
24.
Soussi Gounni A, Lamkhioued B, Morita M, Aldebert D, Sarfati M, Capron A, Capron M: Molecular characterization of the low affinity IgE receptor FcεRII/CD23 expressed by human eosinophils. Int Immunol 1998;10:395–404.
25.
Soussi Gounni A, Lamkhioued B, Ochiai K, Tanaka Y, Delaporte E, Capron A, Kinet JP, Capron M: High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature 1994;367:183–186.
26.
De Andres B, Rakasz E, Hagen M, McCormik ML, Mueller AL, Elliot D, Metwali A, Sandor M, Britigan ME, Weinstock JV, Lynch RG: Lack of Fc-epsilon receptors on murine eosinophils: Implications for the functional significance of elevated IgE and eosinophils in parasitic infections. Blood 1997;89:3826–3836.
27.
Dombrowicz D, Lin S, Flamand V, Koller BH, Kinet JP: Allergy-associated FcRβ is a molecular amplifier of IgE and IgG mediated in vivo responses. Immunity 1998;8:517–529.
28.
Maurer D, Fiebiger E, Reininger B, Wolff-Winiski B, Jouvin MH, Kilgus O, Kinet JP, Stingl G: Expression of functional high affinity immunoglobulin E receptors (FcεRI) on monocytes of atopic individuals. J Exp Med 1994;179:745–750.
29.
Dombrowicz D, Quatannens B, Papin JP, Capron A, Capron M: Expression of a functional Fc epsilon R on rat eosinophils and macrophages. J Immunol 2000;165:1266–1271.
30.
Gould H, Sutton B, Edmeades R, Beavil A: CD23/FcεRII: C-type lectin membrane protein with a split personality; in Gordon J (ed): Monogr Allergy. Basel, Karger, 1991, vol 29, pp 28–49.
31.
Aubry JP, Pochon S, Graber P, Jansen KU, Bonnefoy JY: CD21 is a ligand for CD23 and regulates IgE production. Nature 1992;358:505–507.
32.
Stief A, Texido G, Sansig G, Eibel H, Le Gros G, Van Der Putten H: Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development. J Immunol 1994;152:3378–3390.
33.
Yu P, Kosco-Vilbois M, Richards M, Köhler G, Lamers MC: Negative feedback regulation of IgE synthesis by murine CD23. Nature 1994;369:753–756.
34.
Dombrowicz D, Woerly G, Capron M: IgE receptors on human eosinophils. Chem Immunol 2000;76:63–76.
35.
Auriault C, Gras-Masse H, Pierce RJ, Butterworth AE, Wolowczuk I, Capron M, Ouma JH, Balloul JM, Khalife J, Neyrinck JL, Tartar A, Koech D, Capron A: Antibody response of Schistosoma mansoni infected human subjects to the recombinant P28 glutathione-S-transferase and to synthetic peptides. J Clin Microbiol 1990;98:1918–1924.
36.
Demeure CE, Rihet P, Abel L, Ouattara M, Bourgois A, Dessein AJ: Resistance to Schistosoma mansoni in humans: Influence of IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. J Infect Dis 1993;168:1000–1008.
37.
Gascan H, Gauchat JF, Aversa G, Van Vlasselaer P, deVries JE: Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signalling pathways. J Immunol 1991;147:8–13.
38.
Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K: Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998;102:98–106.
39.
Pretolani M, Goldman M: IL-10: A potential therapy for allergic inflammation. Immunol Today 1997;18:277–280.
40.
Grezel D, Capron M, Grzych JM, Fontaine J, Lecocq JP, Capron A: Protective immunity induced in rat schistosomiasis by a single dose of the Sm28GST recombinant antigen: Effector mechanisms involving IgE and IgA antibodies. Eur J Immunol 1993;23:455–460.
41.
Grzych JM, Grezel D, Xu CB, Neyrinck JL, Capron M, Ouma JH, Butterworth AE, Capron A: IgA antibodies to a protective antigen in human Schistosomiasis mansoni. J Immunol 1993;150:527–535.
42.
Grzych JM, De Bont J, Liu J, Neyrinck JL, Fontaine J, Vercruysse J, Capron A: Relationship of impairment of schistosome 28-kilodalton glutathione S-transferase (GST) activity to expression of immunity to Schistosoma mattheei in calves vaccinated with recombinant Schistosoma bovis 28-kilodalton GST. Infect Immun 1998;66:1142–1148.
43.
Boulanger D, Warter A, Sellir B, Lindner V, Pierce RJ, Chippaux JP, Capron A: Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge. Vaccine 1998;17:319–326.
44.
Remoué F, Rogerie F, Gallissot MC, Guyatt HL, Neyrinck JL, Diakkhate MM, Niang M, Butterworth AE, Auriault C, Capron A, Riveau G: Sex-dependent neutralizing antibodies response to Schistosoma mansoni 28GST vaccinal antigen in infected human population. J Infect Dis 2000;181:1855–1859.
45.
Remoué F, ToVan D, Schacht A, Picquet M, Garraud O, Vercruysse J, Ly A, Capron A, Riveau G: Gender-dependent specific immune response during chronic human Schistosomiasis haematobia. Clin Exp Immunol, in press.
46.
Balloul JM, Sondermeyer P, Dreyer D, Capron M, Grzych JM, Pierce RJ, Carvallo D, Lecocq JP, Capron A: Molecular cloning of a protective antigen of schistosomes. Nature 1987;326:149–153.
47.
Trottein F, Vaney MC, Bachet B, Pierce RJ, Colloc’h N, Lecocq JP, Capron A, Mornon JP: Crystallisation and preliminary X-ray diffraction studies of a protective cloned 28kDa glutathione S-transferase from Schistosoma mansoni. J Mol Biol 1992;224:515–518.
48.
McNair AT, Dissous C, Duvaux-Miret O, Capron A: Cloning and characterisation of the gene encoding the 28 kDa glutathione S-transferase of Schistosoma mansoni. Gene 1993;124:245–249.
49.
Capron A, Riveau G, Grzych JM, Boulanger D, Capron M, Pierce RJ: Development of a vaccine strategy against human and bovine schistosomiasis background and update. Trop Geogr Med 1994;46:242–246.
50.
Boulanger D, Reid GD, Sturrock RF, Wolowczuk I, Balloul JM, Grezel D, Pierce RJ, Otieno MF, Guerret S, Grimaud JA, et al: Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni. Parasite Immunol 1991;13:473–490.
51.
Xu CB, Verwaerde C, Grzych JM, Fontaine J, Capron A: A monoclonal antibody blocking the Schistosoma mansoni 28 kDa glutathione S-transferase activity reduces female worm fecundity and egg viability. Eur J Immunol 1991;21:1801–1807.
52.
Bushara HO, Bashir ME, Malik KH, Mukhtar MM, Trottein F, Capron A, Taylor MG: Suppression of Schistosoma bovis egg production in cattle by vaccination with either glutathione S-transferase or keyhole limpet haemocyanin. Parasite Immunol 1993;15:383–390.
53.
Xu CB, Verwaerde C, Gras-Masse H, Fontaine J, Bossus M, Trottein F, Wolowczuk I, Tartar A, Capron A: Schistosoma mansoni 28 kDa glutathione S-transferase and immunity against parasite fecundity and egg viability. Role of the amino and carboxyl terminal domains. J Immunol 1993;150:940–949.
54.
Trottein F, Godin C, Pierce RJ, Sellin B, Taylor MG, Gorillot I, Silva MS, Lecocq JP, Capron A: Inter-species variation of schistosome 28 kDa glutathione S-transferase. Mol Biochem Parasitol 1992;54:63–72.
55.
Boulanger D, Walter A, Trottein F, Mauny F, Bremond P, Audibert F, Couret D, Kadri S, Godin C, Sellin E, et al: Vaccination of patas monkeys experimentally infected with Schistosoma haematobium using a recombinant glutathione S-transferase cloned from S. mansoni. Parasite Immunol 1995;17:361–369.
56.
Boulanger D, Warter A, Sellin B, Lindner, V, Pierce RJ, Chippaux JP, Capron A: Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge. Vaccine 1998;17:319–326.
57.
De Bont J, Vercruysse J, Grzych JM, Meeus PFM, Capron A: Potential of a recombinant Schistosoma bovis derived glutathione S-transferase to protect cattle against experimental and natural S. mattheei infection. Parasitology 1997;115:249–255.
58.
Capron A: Schistosomiasis: Forty years’ war on the worm. Parasitol Today 1998;14:379–384.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.