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Title: Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae

Abstract

The humoral immune response of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. The binding observed with antibodies of mice vaccinated twice with radiation-attenuated cercariae over a period of 7 to 11 wk was less than 50% of the binding observed with antibodies of mice patently infected for 20 wk, but three to four times greater than that obtained with antibodies of mice infected for 6 wk, irrespective of whether the test extracts were derived from schistosomula or adult worms. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with sulfur-35 methionine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by the sera of infected mice. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.

Authors:
; ; ;
Publication Date:
Research Org.:
Johns Hopkins Univ., Baltimore, MD (USA). School of Medicine
OSTI Identifier:
6408797
Report Number(s):
AD-A-179688/7/XAB
Resource Type:
Technical Report
Resource Relation:
Other Information: Pub. in Journal of Immunology, Vol. 136, No. 12, 4689-4694(15 Jun 1986)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANTIBODIES; IMMUNE REACTIONS; RADIOIMMUNOASSAY; MICE; RADIOPROTECTIVE SUBSTANCES; ADULTS; ANTIGENS; GLUCOPROTEINS; IMMUNITY; IRRADIATION; PLATYHELMINTHS; AGE GROUPS; ANIMALS; CARBOHYDRATES; DRUGS; HELMINTHS; IMMUNOASSAY; IMMUNOLOGY; ISOTOPE APPLICATIONS; MAMMALS; ORGANIC COMPOUNDS; PROTEINS; RADIOASSAY; RADIOIMMUNOLOGY; RODENTS; SACCHARIDES; TRACER TECHNIQUES; VERTEBRATES 560130* -- Radiation Effects on Microorganisms; 560152 -- Radiation Effects on Animals-- Animals

Citation Formats

Dalton, J.P., Strand, M., Mangold, B.L., and Dean, D.A.. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae. United States: N. p., 1986. Web.
Dalton, J.P., Strand, M., Mangold, B.L., & Dean, D.A.. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae. United States.
Dalton, J.P., Strand, M., Mangold, B.L., and Dean, D.A.. 1986. "Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae". United States. doi:.
@article{osti_6408797,
title = {Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae},
author = {Dalton, J.P. and Strand, M. and Mangold, B.L. and Dean, D.A.},
abstractNote = {The humoral immune response of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. The binding observed with antibodies of mice vaccinated twice with radiation-attenuated cercariae over a period of 7 to 11 wk was less than 50% of the binding observed with antibodies of mice patently infected for 20 wk, but three to four times greater than that obtained with antibodies of mice infected for 6 wk, irrespective of whether the test extracts were derived from schistosomula or adult worms. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with sulfur-35 methionine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by the sera of infected mice. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = 1986,
month = 6
}

Technical Report:
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  • The humoral immune responses of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with (/sup 35/S) methinonine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by sera of infected mice. In contrast, sera of vaccinated mice uniquely precipitated a 38,000 m.w. glycoprotein of schistosomula cultured for 5 daysmore » and a 94,000 m.w. glycoprotein of adult male worms. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. In particular, an egg glycoprotein of 85,000 to 70,000 and isoelectric point of 4.8 showed an enhanced reactivity with sera of vaccinated mice in comparison with infected mice. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.« less
  • Surface components of mechanically transformed schistosomula of Schistosoma mansoni were labeled by lactoperoxidase-catalyzed iodination. After solubilization with Triton X-100, antigens were identified by immunoprecipitation. Serum from chronically infected Swiss mice reproducibly precipitated seven major polypeptides with approximate molecular weights (X 10/sup 3/) of 94, 68, 45, 40 to 32, 22, and 16. The antigens of molecular weights (X 10/sup 3/) of 94, 40 to 32, 22, and 16 were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. Sera from several strains of infected inbred mice precipitated the same polypeptides. The antibodiesmore » produced during chronic infection were found to be stimulated by adult worms since sera from 6-week-infected animals precipitated none of the surface antigens, and the pattern produced by precipitation with antibodies from a mouse infected with male worms only was indistinguishable from the pattern obtained with sera from mice with bisexual infections. Antibodies from mice immunized with highly irradiated cercariae reproducibly precipitated major polypeptides of approximately (X 10/sup 3/) 94, 68, 45, 32, 22, 19, and 15 daltons. The antigens of (X 10/sup 3/) 94, 43, 32, 22, and 15 daltons were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. The 15 X 10(3)-dalton surface protein was recognized by sera from vaccinated, but not chronically infected, mice, suggesting that it represents a stage-specific immunogen present on schistosomula but not on adult worms. Sera from two inbred strains of mice which develop different degrees of immunity recognized the same antigens.« less
  • Experiments were performed to compare the migration and survival of 75Se-labeled schistosomes, introduced by percutaneous cercarial exposure or by intravascular administration of 7-day-old lung stage schistosomula, in control and irradiated cercaria-immunized mice. Schistosomula were intravascularly introduced into the lungs, systemic organs and liver by injection via the femoral vein (FV), left ventricle (LV), and superior mesenteric vein (SMV), respectively. The fate of challenge larvae was examined by autoradiography of host tissues and by recovery of adult worms. It was found that both normal and immune elimination were site-dependent. In control mice 45%-60% of cercarial penetrants and lung schistosomula injected intomore » the FV and LV were recoverable as adult worms, while a significantly greater number (70%-85%) were recoverable when lung schistosomula were injected into the SMV. In immunized mice, parasites introduced as either cercariae or FV-injected schistosomula were both highly sensitive to immune elimination. LV-injected schistosomula were also sensitive but to a slightly lesser degree. In contrast, schistosomula placed directly in the liver by SMV injection were totally insensitive to immune elimination. It was concluded that elimination of schistosomula in irradiated cercaria-immunized mice occurs in the lungs and/or in the systemic organs, but not in the liver. Also, it was concluded that immune elimination is not a rapid process, since more than 7 days were required after intravascular challenge for the development of demonstrable differences between control and immunized mice.« less
  • Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnesticmore » circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.« less
  • Mice protected against Shistosoma mansoni infection by intradermal (i.d.) vaccination with nonliving schistosomula or soluble extracts of larval or adult schistosomes (SCHLARP and SWAP, respectively) produce antibodies that react by Western blot analysis with one antigen of M/sub r/ (x 10/sup -3/) 97 in SWAP prepared in the presence of protease inhibitors and two antigens of M/sub r/ (x 10/sup -3/) 95 and 78 in SWAP prepared in their absence. Vaccine antibodies also immunoprecipitated a single 97k molecule, with a pI of 5.5, from detergent extracts of (/sup 35/S)methionine-labeled schistosomes. Three hybridomas, produced from spleen cells of i.d. immunized mice,more » all recognized both the 95k/78k doublet and one 97k antigen, indicating that the two lower M/sub r/ components are degradation products of the same 97k molecule. /sup 125/I-concanavalin a bound weakly to purified Sm-97, indicating that this antigen is minimally glycosylated. Competitive radioimmunoassays performed with /sup 125/I-labeled monoclonal antibodies and purified antigen defined at least two distinct epitopes on Sm-97. Antibodies from i.d. vaccinated mice recognized both monoclonal antibody-defined epitopes, whereas anti-Sm-97 antibodies in chronic infection sera recognized neither. Finally, purified Sm-97 was shown to elicit delayed-type hypersensitivity in i.d. vaccinated mice, suggesting that this molecule is also capable of evoking cell-mediated responses, a finding consistent with its proposed function as a vaccine immunogen.« less