Candidate vaccine antigens identified by antibodies from mice vaccinated with 15- or 50-kilorad-irradiated cercariae of Schistosoma mansoni.
In murine schistosomiasis, the highest levels of resistance to cercarial challenge are obtained by vaccination with radiation-attenuated cercariae. To identify candidate vaccine antigens relevant to the vaccine model, we examined parasite antigens recognized by antibodies from mice vaccinated with irradiated cercariae of Schistosoma mansoni. To optimize recognition of a wide spectrum of antigens, several factors that influence the level of protection in this model were varied; specifically, we examined the effect of (i) single versus multiple vaccinations with irradiated cercariae, (ii) the dose of irradiation (15 or 50 kilorads) administered to the cercariae, and (iii) the genetic background of mouse strains, high-responder (C57BL/6J) versus moderate-responder (CBA/J) mice. We found that the number of vaccinations did not alter antibody specificity but modified the relative antibody titers against particular antigens. The dose of irradiation used to attenuate the immunizing cercariae had a similar effect on antibody titers but in addition influenced antibody specificity. Only mice that had been vaccinated with moderately irradiated cercariae recognized cathepsin B (Sm31) and Sm32. Interestingly, when vaccinated mice of the two strains, C57BL/6J and CBA/J, were compared, differences in antibody responses to particular antigens were observed. Both strains recognized the integral membrane protein Sm23, glutathione S-transferase, and cathepsin B, whereas Sm32 and paramyosin were recognized only by CBA/J mice, and heat shock protein 70 was recognized exclusively by C57BL/6J mice. In this study, we conclusively identified six distinct antigens that are specifically recognized by the humoral immune response of vaccinated mice.
Richter
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Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115.
Harn
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D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D000918:Antibody Specificity; D000947:Antigens, Helminth / Q000276:immunology*; D015153:Blotting, Western; D002401:Cathepsin B / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005982:Glutathione Transferase / Q000276:immunology / Q000302:isolation & purification; D006360:Heat-Shock Proteins / Q000276:immunology / Q000302:isolation & purification; D007814:Larva / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D014335:Tropomyosin / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D006360:Heat-Shock Proteins; D014335:Tropomyosin; D014613:Vaccines, Attenuated; C067614:antigen Sm23, Schistosoma; D005982:Glutathione Transferase; D002401:Cathepsin B