Induction of a protection against S. mansoni with a MAP containing epitopes of Sm37-GAPDH and Sm10-DLC. Eect of coadsorbtion with GM-CSF on alum Laurent Argiro, Sandrine Henri, He´lia Dessein, Bourema Kouriba, Alain J. Dessein, Alain Bourgois* Laboratory of Immunology and Genetics of Parasitic Diseases INSERM U399, Faculte´ de Me´decine, Universite´ de la Me´diterrane´e, 27 bd Jean Moulin, 13385 Marseille Cedex 5, France Received 17 June 1999; received in revised form 13 October 1999; accepted 25 October 1999 Abstract Studies of anti-S. mansoni immunological responses in individuals living in endemic areas identified immunogens (Sm37- GAPDH and Sm10-DLC) with vaccine candidate properties. Analysis of the epitopes of these immunogens indicated that: (i) Sm37-5 is a major B-cell epitope of Sm37-GAPDH and the IgG antibody reactivity toward this determinant is associated with resistance to reinfection; (ii) Sm10-T is a T-cell epitope of the major T-cell immunogen Sm10-DLC. This led us to test a multiple antigen peptide (MAP) containing Sm37-5 and Sm10-T as an anti-schistosome vaccine. This MAP induced a significant protective immune response in mice when injected in Freund’s adjuvant or coadsorbed with GM–CSF on aluminium hydroxide. In the latter case the physical link between the cytokine and the antigen via the coadsorption on alum was necessary to obtain a protective response. Results of the antibody response indicated that when the MAP and GM–CSF were coadsorbed on alum, the antibody response against the Sm10-T epitope located in the NH 2 -terminal position was significantly amplified up to 30% of the anti-Sm37-5 response. 7 2000 Elsevier Science Ltd. All rights reserved. Keywords: Schistosomiasis; Vaccination; Cytokine; MAP 1. Introduction Schistosomiasis aects more than 200 million people in subtropical countries and several laboratories have identified S. mansoni antigens with vaccine candidate properties (reviewed in Ref. [1]). Two of them, Sm37- GAPDH [2] and Sm10-DLC [3,4], were identified in studies on the immunological responses of humans naturally sensitized in an endemic area [5,6]. Sm37-gly- ceraldehyde-3-phosphate dehydrogenase (GAPDH) is a membrane larval antigen of Schistosoma mansoni [2]. We previously observed in a population living in an area endemic for S. mansoni that adolescents who resisted reinfection after treatment, had mounted a sig- nificantly higher IgG antibody response against this antigen than adolescents reinfected within 2 years after treatment [5]. This protein was then considered as a good candidate for a vaccine against human schistoso- miasis [1,7]. Analysis of the antigenic determinants on Sm37-GAPDH revealed five B-cell epitopes and two T-cell epitopes. Among them, a major B cell epitope, Sm37-5, was preferentially recognized by IgG from re- sistant adolescents compared to susceptible ones as found for the whole molecule (Argiro et al., submitted Vaccine 18 (2000) 2033–2038 0264-410X/00/$ - see front matter 7 2000 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(99)00523-X www.elsevier.com/locate/vaccine * Corresponding author. Tel.: +33-491-32-45-25; fax: +33-491-79- 60-63. E-mail address: bourgois@voltaire.timone.univ-mrs.fr (A. Bourgois). Abbreviations: GAPDH, glyceraldehyde-3-phosphate dehydrogen- ase; DLC, dynein light chain; GM–CSF, granulocyte-macrophage colony stimulating factor; MAP, multiple antigenic peptide; OVA, ovalbumin; BGG, bovine gamma globulin.