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. 1993 Jan;61(1):146–154. doi: 10.1128/iai.61.1.146-154.1993

Candidate vaccine antigens identified by antibodies from mice vaccinated with 15- or 50-kilorad-irradiated cercariae of Schistosoma mansoni.

D Richter 1, D A Harn 1
PMCID: PMC302699  PMID: 8418037

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balloul J. M., Grzych J. M., Pierce R. J., Capron A. A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. J Immunol. 1987 May 15;138(10):3448–3453. [PubMed] [Google Scholar]
  2. Bickle Q. D., Sacko M., Vignali D. A. Induction of immunity against Schistosoma mansoni by drug (Ro11-3128)-terminated infections: analysis of surface antigen recognition. Parasite Immunol. 1990 Nov;12(6):569–586. doi: 10.1111/j.1365-3024.1990.tb00989.x. [DOI] [PubMed] [Google Scholar]
  3. Chappell C. L., Dresden M. H. Antibody response to a purified parasite proteinase (SMw32) in Schistosoma mansoni infected mice. Am J Trop Med Hyg. 1988 Jul;39(1):66–73. doi: 10.4269/ajtmh.1988.39.66. [DOI] [PubMed] [Google Scholar]
  4. Chappell C. L., Dresden M. H., Gryseels B., Deelder A. M. Antibody response to Schistosoma mansoni adult worm cysteine proteinases in infected individuals. Am J Trop Med Hyg. 1990 Apr;42(4):335–341. doi: 10.4269/ajtmh.1990.42.335. [DOI] [PubMed] [Google Scholar]
  5. Chappell C. L., Dresden M. H. Purification of cysteine proteinases from adult Schistosoma mansoni. Arch Biochem Biophys. 1987 Aug 1;256(2):560–568. doi: 10.1016/0003-9861(87)90613-8. [DOI] [PubMed] [Google Scholar]
  6. Chappell T. G., Konforti B. B., Schmid S. L., Rothman J. E. The ATPase core of a clathrin uncoating protein. J Biol Chem. 1987 Jan 15;262(2):746–751. [PubMed] [Google Scholar]
  7. Correa-Oliveira R., Sher A., James S. L. Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. I. Analysis of antibody responses. J Immunol. 1984 Sep;133(3):1581–1586. [PubMed] [Google Scholar]
  8. Coulson P. S., Mountford A. P. Fate of attenuated schistosomula administered to mice by different routes, relative to the immunity induced against Schistosoma mansoni. Parasitology. 1989 Aug;99(Pt 1):39–45. doi: 10.1017/s003118200006100x. [DOI] [PubMed] [Google Scholar]
  9. Dalton J. P., Strand M. Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae. J Immunol. 1987 Oct 1;139(7):2474–2481. [PubMed] [Google Scholar]
  10. Davis A. H., Nanduri J., Watson D. C. Cloning and gene expression of Schistosoma mansoni protease. J Biol Chem. 1987 Sep 15;262(26):12851–12855. [PubMed] [Google Scholar]
  11. Delgado V., McLaren D. J. Evidence for enhancement of IgG1 subclass expression in mice polyvaccinated with radiation-attenuated cercariae of Schistosoma mansoni and the role of this isotype in serum-transferred immunity. Parasite Immunol. 1990 Jan;12(1):15–32. doi: 10.1111/j.1365-3024.1990.tb00933.x. [DOI] [PubMed] [Google Scholar]
  12. Dresden M. H., Deelder A. M. Schistosoma mansoni: thiol proteinase properties of adult worm "hemoglobinase". Exp Parasitol. 1979 Oct;48(2):190–197. doi: 10.1016/0014-4894(79)90098-5. [DOI] [PubMed] [Google Scholar]
  13. Flanigan T. P., King C. H., Lett R. R., Nanduri J., Mahmoud A. A. Induction of resistance to Schistosoma mansoni infection in mice by purified parasite paramyosin. J Clin Invest. 1989 Mar;83(3):1010–1014. doi: 10.1172/JCI113942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harn A. Immunization with schistosome membrane antigens. Acta Trop Suppl. 1987 Jun;12:46–49. [PubMed] [Google Scholar]
  15. Harn D. A., Mitsuyama M., David J. R. Schistosoma mansoni. Anti-egg monoclonal antibodies protect against cercarial challenge in vivo. J Exp Med. 1984 May 1;159(5):1371–1387. doi: 10.1084/jem.159.5.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harn D. A., Mitsuyama M., Huguenel E. D., David J. R. Schistosoma mansoni: detection by monoclonal antibody of a 22,000-dalton surface membrane antigen which may be blocked by host molecules on lung stage parasites. J Immunol. 1985 Sep;135(3):2115–2120. [PubMed] [Google Scholar]
  17. Hazdai R. T., Levi-Schaffer F., Brenner V., Horowitz S., Eshhar Z., Arnon R. Protective monoclonal antibody against Schistosoma mansoni: antigen isolation, characterization, and suitability for active immunization. J Immunol. 1985 Oct;135(4):2772–2779. [PubMed] [Google Scholar]
  18. Hedstrom R., Culpepper J., Harrison R. A., Agabian N., Newport G. A major immunogen in Schistosoma mansoni infections is homologous to the heat-shock protein Hsp70. J Exp Med. 1987 May 1;165(5):1430–1435. doi: 10.1084/jem.165.5.1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hedstrom R., Culpepper J., Schinski V., Agabian N., Newport G. Schistosome heat-shock proteins are immunologically distinct host-like antigens. Mol Biochem Parasitol. 1988 Jun;29(2-3):275–282. doi: 10.1016/0166-6851(88)90082-5. [DOI] [PubMed] [Google Scholar]
  20. Hsü S. Y., Hsü H. F., Burmeister L. F. Schistosoma mansoni: vaccination of mice with highly x-irradiated cercariae. Exp Parasitol. 1981 Aug;52(1):91–104. doi: 10.1016/0014-4894(81)90065-5. [DOI] [PubMed] [Google Scholar]
  21. James S. L. Induction of protective immunity against Schistosoma mansoni by a non-living vaccine. V. Effects of varying the immunization and infection schedule and site. Parasite Immunol. 1987 Sep;9(5):531–541. doi: 10.1111/j.1365-3024.1987.tb00528.x. [DOI] [PubMed] [Google Scholar]
  22. James S. L., Labine M., Sher A. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. I. Analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity. Cell Immunol. 1981 Nov 15;65(1):75–83. doi: 10.1016/0008-8749(81)90053-8. [DOI] [PubMed] [Google Scholar]
  23. James S. L., Pearce E. J. The influence of adjuvant on induction of protective immunity by a non-living vaccine against schistosomiasis. J Immunol. 1988 Apr 15;140(8):2753–2759. [PubMed] [Google Scholar]
  24. James S. L., Salzman C., Pearce E. J. Induction of protective immunity against Schistosoma mansoni by a non-living vaccine. VI. Antigen recognition by non-responder mouse strains. Parasite Immunol. 1988 Jan;10(1):71–83. doi: 10.1111/j.1365-3024.1988.tb00204.x. [DOI] [PubMed] [Google Scholar]
  25. James S. L., Sher A. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae III. Identification of a mouse strain, P/N, that fails to respond to vaccination. Parasite Immunol. 1983 Nov;5(6):567–575. doi: 10.1111/j.1365-3024.1983.tb00773.x. [DOI] [PubMed] [Google Scholar]
  26. Jwo J., LoVerde P. T. The ability of fractionated sera from animals vaccinated with irradiated cercariae of Schistosoma mansoni to transfer immunity to mice. J Parasitol. 1989 Apr;75(2):252–260. [PubMed] [Google Scholar]
  27. Kelly E. A., Colley D. G. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance. J Immunol. 1988 Apr 15;140(8):2737–2745. [PubMed] [Google Scholar]
  28. King C. H., Lett R. R., Nanduri J., el Ibiary S., Peters P. A., Olds G. R., Mahmoud A. A. Isolation and characterization of a protective antigen for adjuvant-free immunization against Schistosoma mansoni. J Immunol. 1987 Dec 15;139(12):4218–4224. [PubMed] [Google Scholar]
  29. Klinkert M. Q., Felleisen R., Link G., Ruppel A., Beck E. Primary structures of Sm31/32 diagnostic proteins of Schistosoma mansoni and their identification as proteases. Mol Biochem Parasitol. 1989 Mar 1;33(2):113–122. doi: 10.1016/0166-6851(89)90025-x. [DOI] [PubMed] [Google Scholar]
  30. Klinkert M. Q., Ruppel A., Beck E. Cloning of diagnostic 31/32 kilodalton antigens of Schistosoma mansoni. Mol Biochem Parasitol. 1987 Oct;25(3):247–255. doi: 10.1016/0166-6851(87)90088-0. [DOI] [PubMed] [Google Scholar]
  31. Klinkert M. Q., Ruppel A., Felleisen R., Link G., Beck E. Expression of diagnostic 31/32 kilodalton proteins of Schistosoma mansoni as fusions with bacteriophage MS2 polymerase. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):233–239. doi: 10.1016/0166-6851(88)90042-4. [DOI] [PubMed] [Google Scholar]
  32. Laclette J. P., Shoemaker C. B., Richter D., Arcos L., Pante N., Cohen C., Bing D., Nicholson-Weller A. Paramyosin inhibits complement C1. J Immunol. 1992 Jan 1;148(1):124–128. [PubMed] [Google Scholar]
  33. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  34. Lanar D. E., Pearce E. J., James S. L., Sher A. Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice. Science. 1986 Oct 31;234(4776):593–596. doi: 10.1126/science.3094144. [DOI] [PubMed] [Google Scholar]
  35. Landsperger W. J., Stirewalt M. A., Dresden M. H. Purification and properties of a proteolytic enzyme from the cercariae of the human trematode parasite Schistosoma mansoni. Biochem J. 1982 Jan 1;201(1):137–144. doi: 10.1042/bj2010137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lazdins J. K., Stein M. J., David J. R., Sher A. Schistosoma mansoni: rapid isolation and purification of schistosomula of different developmental stages by centrifugation on discontinuous density gradients of Percoll. Exp Parasitol. 1982 Feb;53(1):39–44. doi: 10.1016/0014-4894(82)90090-x. [DOI] [PubMed] [Google Scholar]
  37. Lewis F. A., Wilson E. M. Schistosoma mansoni: splenic lymphocyte responses of mice after initial exposure to highly irradiated cercariae. Exp Parasitol. 1982 Aug;54(1):21–32. doi: 10.1016/0014-4894(82)90106-0. [DOI] [PubMed] [Google Scholar]
  38. Mangold B. L., Dean D. A. Passive transfer with serum and IgG antibodies of irradiated cercaria-induced resistance against Schistosoma mansoni in mice. J Immunol. 1986 Apr 1;136(7):2644–2648. [PubMed] [Google Scholar]
  39. Mangold B. L., Dean D. A. The migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host-parasite contact in relation to the induction of resistance in mice. Parasitology. 1984 Apr;88(Pt 2):249–265. [PubMed] [Google Scholar]
  40. Matsumoto Y., Perry G., Levine R. J., Blanton R., Mahmoud A. A., Aikawa M. Paramyosin and actin in schistosomal teguments. Nature. 1988 May 5;333(6168):76–78. doi: 10.1038/333076a0. [DOI] [PubMed] [Google Scholar]
  41. Minard P., Dean D. A., Jacobson R. H., Vannier W. E., Murrell K. D. Immunization of mice with cobalt-60 irradiated Schistosoma mansoni cercariae. Am J Trop Med Hyg. 1978 Jan;27(1 Pt 1):76–86. doi: 10.4269/ajtmh.1978.27.76. [DOI] [PubMed] [Google Scholar]
  42. Minard P., Dean D. A., Vannier W. E., Murrell K. D. Effect of immunization on migration of Schistosoma mansoni through lungs. Am J Trop Med Hyg. 1978 Jan;27(1 Pt 1):87–93. doi: 10.4269/ajtmh.1978.27.87. [DOI] [PubMed] [Google Scholar]
  43. Mountford A. P., Coulson P. S., Wilson R. A. Antigen localization and the induction of resistance in mice vaccinated with irradiated cercariae of Schistosoma mansoni. Parasitology. 1988 Aug;97(Pt 1):11–25. doi: 10.1017/s0031182000066701. [DOI] [PubMed] [Google Scholar]
  44. Mountford A. P., Wilson R. A. Schistosoma mansoni: the effect of regional lymphadenectomy on the level of protection induced in mice by radiation-attenuated cercariae. Exp Parasitol. 1990 Nov;71(4):463–469. doi: 10.1016/0014-4894(90)90072-k. [DOI] [PubMed] [Google Scholar]
  45. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  46. Oligino L. D., Percy A. J., Harn D. A. Purification and immunochemical characterization of a 22 kilodalton surface antigen from Schistosoma mansoni. Mol Biochem Parasitol. 1988 Mar;28(2):95–103. doi: 10.1016/0166-6851(88)90056-4. [DOI] [PubMed] [Google Scholar]
  47. Pearce E. J., James S. L., Dalton J., Barrall A., Ramos C., Strand M., Sher A. Immunochemical characterization and purification of Sm-97, a Schistosoma mansoni antigen monospecifically recognized by antibodies from mice protectively immunized with a nonliving vaccine. J Immunol. 1986 Dec 1;137(11):3593–3600. [PubMed] [Google Scholar]
  48. Pearce E. J., James S. L., Hieny S., Lanar D. E., Sher A. Induction of protective immunity against Schistosoma mansoni by vaccination with schistosome paramyosin (Sm97), a nonsurface parasite antigen. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5678–5682. doi: 10.1073/pnas.85.15.5678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Reynolds S. R., Harn D. A. Comparison of irradiated-cercaria schistosome vaccine models that use 15- and 50-kilorad doses: the 15-kilorad dose gives greater protection, smaller liver sizes, and higher gamma interferon levels after challenge. Infect Immun. 1992 Jan;60(1):90–94. doi: 10.1128/iai.60.1.90-94.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ruppel A., Rother U., Vongerichten H., Lucius R., Diesfeld H. J. Schistosoma mansoni: immunoblot analysis of adult worm proteins. Exp Parasitol. 1985 Oct;60(2):195–206. doi: 10.1016/0014-4894(85)90023-2. [DOI] [PubMed] [Google Scholar]
  51. Scallon B. J., Bogitsh B. J., Carter C. E. Cloning of a Schistosoma japonicum gene encoding a major immunogen recognized by hyperinfected rabbits. Mol Biochem Parasitol. 1987 Jul;24(3):237–245. doi: 10.1016/0166-6851(87)90155-1. [DOI] [PubMed] [Google Scholar]
  52. Sher A., Hieny S., James S. L., Asofsky R. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. II. Analysis of immunity in hosts deficient in T lymphocytes, B lymphocytes, or complement. J Immunol. 1982 Apr;128(4):1880–1884. [PubMed] [Google Scholar]
  53. Simons P. C., Vander Jagt D. L. Purification of glutathione S-transferases from human liver by glutathione-affinity chromatography. Anal Biochem. 1977 Oct;82(2):334–341. doi: 10.1016/0003-2697(77)90169-5. [DOI] [PubMed] [Google Scholar]
  54. Simpson A. J., Hackett F., Walker T., de Rossi R., Smithers S. R. Antibody response against schistosomulum surface antigens and protective immunity following immunization with highly irradiated cercariae of Schistosoma mansoni. Parasite Immunol. 1985 Mar;7(2):133–152. doi: 10.1111/j.1365-3024.1985.tb00065.x. [DOI] [PubMed] [Google Scholar]
  55. Simpson A. J., James S. L., Sher A. Identification of surface antigens of schistosomula of Schistosoma mansoni recognized by antibodies from mice immunized by chronic infection and by exposure to highly irradiated cercariae. Infect Immun. 1983 Aug;41(2):591–597. doi: 10.1128/iai.41.2.591-597.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Smithers S. R., Terry R. J. The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology. 1965 Nov;55(4):695–700. doi: 10.1017/s0031182000086248. [DOI] [PubMed] [Google Scholar]
  57. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Welch W. J., Feramisco J. R. Rapid purification of mammalian 70,000-dalton stress proteins: affinity of the proteins for nucleotides. Mol Cell Biol. 1985 Jun;5(6):1229–1237. doi: 10.1128/mcb.5.6.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Wright M. D., Henkle K. J., Mitchell G. F. An immunogenic Mr 23,000 integral membrane protein of Schistosoma mansoni worms that closely resembles a human tumor-associated antigen. J Immunol. 1990 Apr 15;144(8):3195–3200. [PubMed] [Google Scholar]
  60. Zerda K. S., Dresden M. H., Chappell C. L. Schistosoma mansoni: expression and role of cysteine proteinases in developing schistosomula. Exp Parasitol. 1988 Dec;67(2):238–246. doi: 10.1016/0014-4894(88)90071-9. [DOI] [PubMed] [Google Scholar]

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