Elsevier

Vaccine

Volume 18, Issue 19, 3 April 2000, Pages 2039-2048
Vaccine

Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH

https://doi.org/10.1016/S0264-410X(99)00521-6Get rights and content

Abstract

A previous study performed in adolescents living in an area endemic for Schistosoma mansoni in Brazil has shown that a 37 kDa schistosome surface antigen is a selective target for antibodies in sera from those who were resistant to reinfection. This antigen was shown by molecular cloning to be the schistosome GAPDH. The aim of the present work was to assess whether peptides corresponding to GAPDH antigenic determinants could be used in a subunit vaccine. Five B cell and two T cell epitopic regions were identified on Sm37-GAPDH. One of the B cell determinants (Sm37-5, aa 268–289) is highly antigenic in human infections and antibody reactivity toward this determinant is associated with resistance to reinfection. Mice and rats immunized with Sm37-5 were partially protected against a challenge infection, indicating that this peptide can induce protective immunity. Analysis of Sm37-5 amino acid sequence indicated that this antigenic determinant is likely conserved among other pathogenic strains of schistosome (S. haematobium, S. intercalatum and S. japonicum), although it shows major amino acid differences with the corresponding human GAPDH sequence. All together these results indicate that Sm37-5 should be considered as a candidate component for an anti-schistosome subunit vaccine.

Introduction

Five to fifteen percent of subjects infected by Schistosoma mansoni develop a severe hepatosplenic disease that may be fatal if left untreated [1]. As many water-borne diseases, schistosomiasis is spreading in developing countries where irrigation programs are implemented to sustain agriculture development. Although infections can be cured by schistosomicides, chemotherapy is not appropriate for the long-term control of this endemy and a major WHO objective is the development of a vaccine against schistosomiasis [2]. For practical, economical and safety reasons, the ideal vaccine must be a sub-unit one and many research efforts are focused on the identification of schistosome molecules that could be included in the vaccine. This search is carried out along two complementary lines in animal models and in epidemiological studies in human populations. Antigens have been looked for in murine experimental models of schistosomiasis using protective monoclonal or polyclonal antibodies; some of these antigens were shown to induce protection in mice and/or rats against challenges by schistosome cercariae [3], [4], [5], [6], [7], [8], [9], [10], [11]. Protective levels were comprised between 20 and 50%. The reasons why full protection could not be reached in animals are unknown, this may have to do with some particularities of the mouse and rat experimental models.

In the past decade, various observations indicated that certain humans living in endemic areas of S. mansoni exhibit high level of anti-schistosome immunity that is close to full protection for certain subjects [12], [13]. These findings led our group and others to attempt to identify vaccinating antigens among the major antigens recognized by antibodies and T cells from resistant individuals. It was also hoped that this strategy would lead to the selection of molecules capable of inducing a protective immune response that would be efficiently recalled by natural infections. Along these lines, our laboratory has identified and characterized the schistosome Sm37-GAPDH [13], [14] and Sm10-DLC [15], [16] molecules as major targets respectively of antibodies and T cells from resistant subjects. The aims of the present work was to evaluate whether peptides corresponding to antigenic determinants on schistosome GAPDH could be valid candidates to a subunit vaccine.

Section snippets

Reagents

BSA, Tween 20, NBT-BCIP (nitro blue tetrazolium-bromo chloro indolyl phosphate) and pNPP (para-nitrophenyl phosphate) were from Sigma Chemicals Co. (St Louis, MO, USA). Alkaline phosphatase-coupled rabbit anti-human IgG, IgG1 and IgG2; alkaline phosphatase-coupled goat anti-mouse IgG; mouse anti-human IgG3, IgG4 and Ig light chain; mouse IgG and human IgG, IgG1, IgG2, IgG3, IgG4 myeloma immunoglobulins were from Immunotech (Marseille, France).

Serum samples

Sera were obtained from 156 individuals aged from 4

Identification of Sm37 B cell epitopic regions

An expression library was constructed from the cDNA coding for Sm37. Fragments were generated by DNAse I digestion and were hence expected to end at all possible random positions. The library was screened with an anti-Sm37 rabbit immune serum. All detected phages were kept for further characterization. Ten of them (A, C, D, E, F, G, H, K, X and Y) were randomly chosen and used to affinity purify specific antibodies from the immune serum. These antibody preparations allowed the definition of

Discussion

Analysis by Western blot and ELISA of the reactivity of schistosome larval surface antigens with antibodies of adolescents from an endemic area showed that a 37 kDa antigen reacted preferentially with sera from subjects who resisted reinfection after chemotherapy [13]. The cDNA of Sm37 was cloned and shown to encode the schistosome glyceraldehyde-3-phosphate dehydrogenase [14]. Since the immunological properties of schistosome GAPDH indicated that it could be the target of protective immunity,

Acknowledgements

This work received financial assistance from INSERM, CNRS, CEE (TS3-CT94-0296) and from the UNDP/World Bank/WHO (920-349) Special Program for Research and Training in Tropical Diseases. L. Argiro was supported by a fellowship from the Conseil Régional PACA.

References (38)

  • S.C. Bourguignon et al.

    Detrimental effect of nitric oxide on Trypanosoma cruzi and Leishmania major life cells

    Acta Tropica

    (1997)
  • UNDP/World Bank/WHO. Schistosomiasis in tropical disease research, Eleventh Programme Report...
  • E.J. Pearce et al.

    Immunochemical characterization and purification of Sm-97, a Schistosoma mansoni antigen monospecifically recognized by antibodies from mice protectively immunized with a nonliving vaccine

    J. Immun.

    (1986)
  • J.M. Balloul et al.

    Molecular cloning of a protective antigen of schistosomes

    Nature

    (1987)
  • J.M. Balloul et al.

    A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis

    J. Immunol.

    (1987)
  • J.P. Dalton et al.

    Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae

    J. Immun.

    (1987)
  • M.D. Wright et al.

    An immunogenic Mr 23,000 integral membrane protein of Schistosoma mansoni worms that closely resembles a human tumor-associated antigen

    J. Immun.

    (1990)
  • L.M. Armory-Soisson et al.

    Induction of protective immunity in mice using a 62-kDa recombinant fragment of a Schistosoma mansoni surface antigen

    J. Immun.

    (1992)
  • S.R. Reynolds et al.

    T and B cell epitope mapping of Sm23, an integral membrane protein of Schistosoma mansoni.

    J. Immun.

    (1992)
  • Cited by (0)

    1

    The first two authors have contributed equally to this work.

    2

    Present address: Institut für Medizinische Virologie, Heidelberg, Germany.

    View full text