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Pathology associated with vaccination against Schistosoma mansoni in mice using cryopreserved radiation-attenuated
Abstract:
Twenty-one mice were injected intramuscularly with 2000 Schistosoma mansoni schistosomula irradiated at 20 krad and cryopreserved; three mice were killed on each of days 0, 2, 5, 9, 19, 28 and 44 days after infection and muscle from the site of injection in the left hind leg, the lungs and livers removed for histological examination. Schistosomula were seen in sections from the leg muscle from days 0 to 19 inclusive, in the lungs from day 2 to day 28 inclusive and in the livers from days 9 to 28 inclusive. Most schistosomula were seen in sections of the leg muscle with considerably fewer parasites occurring in the lungs and especially the livers. Granulomatous reactions comprising eosinophils, polymorphs, plasma cells and macrophages were first seen in the leg muscle on day 2, in the lungs on day 5 and in the liver on day 19. The peak inflammatory reactions appeared to occur between days 5 and 9, 9 and 19 and 28 and 44 respectively in the three tissues. The pathology is discussed in relation to the dose of irradiation required to attenuate the schistosomula for optimal immunogenicity.
Insights
Irradiated Schistosoma mansoni schistosomula were tracked in mice to understand parasite migration and host immune responses. This study informs optimal irradiation doses for developing effective schistosomiasis vaccines.
Area of Science:
- Immunology
- Parasitology
- Veterinary Pathology
Background:
- Schistosomiasis remains a significant global health concern, necessitating effective vaccine strategies.
- Attenuated Schistosoma mansoni parasites are a promising avenue for vaccine development.
- Understanding parasite fate and host immune response post-attenuation is crucial.
Purpose of the Study:
- To investigate the migration patterns and tissue distribution of irradiated Schistosoma mansoni schistosomula in mice.
- To characterize the host inflammatory and granulomatous responses to attenuated parasites in different tissues.
- To correlate parasite presence and host pathology with irradiation dose for optimal immunogenicity.
Main Methods:
- Mice were intramuscularly injected with irradiated (20 krad) and cryopreserved Schistosoma mansoni schistosomula.
- Parasite presence was assessed via histological examination of muscle, lung, and liver tissues at multiple time points (days 0-44).
- Inflammatory and granulomatous reactions were evaluated in the same tissues.
Main Results:
- Schistosomula were detected in leg muscle (days 0-19), lungs (days 2-28), and livers (days 9-28), with the highest parasite burden in the muscle.
- Granulomatous reactions, involving eosinophils, polymorphs, plasma cells, and macrophages, were observed in all tissues, with varying onset and peak times.
- Peak inflammatory responses occurred between days 5-9 in muscle, 9-19 in lungs, and 28-44 in the liver.
Conclusions:
- Irradiated Schistosoma mansoni schistosomula exhibit distinct migration patterns and elicit differential immune responses in host tissues.
- The timing and intensity of inflammatory reactions correlate with parasite location and duration.
- These findings provide critical insights for optimizing irradiation protocols to enhance the immunogenicity of Schistosoma mansoni vaccines.