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Pathology of a Live Attenuated Anti-Schistosome Vaccine in Mice^*

Tissue responses of mice to intramuscular injection of 50 kR ⁶⁰Co-attenuated schistosomula of Schistosoma mansoni were studied. Controls included injection of unattenuated schistosomula, medium alone, antigen-coated beads, and alum-adsorbed tetanus/diphtheria toxoids. Primary reactions to tissue-confined deposits of injected schistosomula, whether attenuated or not, were relatively intense and prolonged. Parasite attrition proceeded steadily, with most destroyed by the 7th day; however, a few intact organisms persisted up to 4 weeks. Cryopreservation did not alter the course of parasite attrition nor host reaction. Irradiated larvae were not found in lymph nodes, lungs, or liver. Neutrophils dominated the early reactions and were gradually replaced by mononuclear phagocytes, lymphoid cells, and eosinophils. Fibroblast proliferation and muscle regeneration began by day 3; reaction size and intensity peaked by day 7. From weeks 1–4, inflammatory infiltrates and regenerative proliferation underwent gradual involution, and injection sites were healed with no scarring by the end of 4–5 weeks. Mice primed by infection or by prior injection showed an accelerated course of inflammation, enhanced tissue eosinophilia, and more rapid healing. An unwanted, but prominent, feature of schistosomular vaccine reactions in mice was tracking of the inflammatory infiltrate along connective tissue septal and nerve sheaths, the latter raising the question of the pain potential of the vaccine. To conclude, in mice, attenuated schistosomular vaccines cause relatively marked local inflammatory responses but no systemic lesions at all, and their injection sites heal without permanent damage.

Accepted for publication June 16, 1982.

^* Supported by grants from the Edna McConnell Clark Foundation (280-0160 and 280-0097) and from the U.S.-Japan Cooperative Medical Science Program, NIAID (AI-02631).

Animals used in this study were maintained in accordance with the guidelines of the Committee on Animals of the Harvard Medical School and those prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council (DHEW publication no. 78-23, revised 1978).

Address reprint requests to: Dr. James E. Byram, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115.