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Title: Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

Abstract

Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals.

Authors:
; ;
Publication Date:
Research Org.:
Biomedical Research Inst., Rockville, MD
OSTI Identifier:
6628989
Resource Type:
Journal Article
Resource Relation:
Journal Name: Exp. Parasitol.; (United States); Journal Volume: 57:3
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; SCHISTOSOMA; FREEZING; INFECTIVITY; RADIOPRESERVATION; VACCINES; CHEMICAL PREPARATION; TESTING; CESIUM 137; COBALT 60; CRYOBIOLOGY; INOCULATION; MICE; SCHISTOSOMIASIS; ALKALI METAL ISOTOPES; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGY; CESIUM ISOTOPES; COBALT ISOTOPES; DISEASES; HELMINTHS; INFECTIOUS DISEASES; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IRRADIATION; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; MAMMALS; MINUTES LIVING RADIOISOTOPES; NUCLEI; ODD-EVEN NUCLEI; ODD-ODD NUCLEI; PARASITIC DISEASES; PLATYHELMINTHS; PRESERVATION; RADIOISOTOPES; RODENTS; SYNTHESIS; TREMATODES; VERTEBRATES; YEARS LIVING RADIOISOTOPES 560134* -- Radiation Effects on Microorganisms-- Vaccine Preparation & Other Applications-- (-1987); 551000 -- Physiological Systems; 070203 -- Radiation Sources-- Use in Medical Supply Sterilization-- (-1987)

Citation Formats

Lewis, F.A., Stirewalt, M.A., and Leef, J.L. Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules. United States: N. p., 1984. Web. doi:10.1016/0014-4894(84)90099-7.
Lewis, F.A., Stirewalt, M.A., & Leef, J.L. Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules. United States. doi:10.1016/0014-4894(84)90099-7.
Lewis, F.A., Stirewalt, M.A., and Leef, J.L. 1984. "Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules". United States. doi:10.1016/0014-4894(84)90099-7.
@article{osti_6628989,
title = {Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules},
author = {Lewis, F.A. and Stirewalt, M.A. and Leef, J.L.},
abstractNote = {Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals.},
doi = {10.1016/0014-4894(84)90099-7},
journal = {Exp. Parasitol.; (United States)},
number = ,
volume = 57:3,
place = {United States},
year = 1984,
month = 6
}
  • Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less
  • The effectiveness of a cryopreserved, irradiated schistosomule vaccine against an homologous Schistosoma mansoni cercarial challenge was tested in C57B1/6 mice. Highly significant levels of protection developed consistently when mice were immunized with the vaccine irradiated at 10-20 Krad, i.e., doses below that considered optimal for irradiated cercariae (50 Krad). Cryopreserved schistosomules irradiated at 10 or 20 Krad induced greater levels of protection than did schistosomules irradiated at 2, 5, 30, or 50 Krad. Protective immunity developed as early as 3 weeks post-immunization. When immunizing inocula were injected at various times post-thaw, or when schistosomule subpopulations of normal-appearing, damaged or deadmore » organisms were injected, those populations which had appeared to sustain the least degree of damage were those most capable of stimulating protective immunity. These findings highlight the hazards of extrapolating conditions considered standard for an irradiated cercarial vaccine to one in which cryopreservation, for storage of the schistosomules, is an added stress.« less