Kathy M Cruise

Analysis of Infection Characteristics and Antiparasite Immune Responses in Resistant Compared with Susceptible Hosts

Variations in susceptibility or immune responsiveness to parasites, and variations in the consequences of parasitic infection, are readily detected in natural host populations (Wakelin 1978a). Variable outcomes of parasitic infection and disease are predictable bearing in mind that genetic heterogeneity of hosts a«c/parasites is essential for evolutionary survival of either party. It has been argued that immunological events have been the key (but certainly not the only) ingredient in the evolutionary development of balanced host-parasite relationships (Sprent 1959, Burnet & White 1972, and reviewed in Mitchell 1979a,b). The animal breeder expects to exploit any high hereditability of resistance to parasites and searches for linked characteristics which are detected readily, or correlative immune responses, to be used in selection programs. Similarly, the experimental immunoparasitologist expects to exploit at least some genetically-based variations in host resistance to pinpoint immunological effector mechanisms and target parasite antigens (and to identify genetic aspects of expression oi both) which are necessary or sufficient for host protection. Of particular interest are differences in (1) disease manifestations, (2) levels and duration of primary infection, (3) responsiveness to vaccination, (4) responsive-

Antibody responses to the antigen Sj26 of Schistosoma japonicum worms that is recognized by genetically resistant 129/J mice.

Summary Serum antibody responses of mice exposed to Philippine isolates of Schistosoma japonicum have been analysed by immunoprecipitation of exogenously radiolabelled antigens extracted from adult worms. Attention was focused on labelled protein antigens differentially recognized by sera of mice that differ genetically in their resistance status. Mice of the inbred strain 129/J can show high level resistance to first or repeated infection with S. japonicum. Even after six percutaneous administrations of 25 cercariae, approximately 50% of 129/J mice remain healthy with no or very feu worms present in the portal system. Sera from 129/J mice exposed to S. japonicum consistently and differentially recognise an antigen of adult worms of mol. wt. 26,000. This antigen, termed Sj26, is not immunoprecipitated from S. mansoni adult worms by sera from resistant 129/J mice. Serum antibodies to Sj26 are present in at least some patients with a history of schistosomiasis japonica. Whether immune responses to SJ26 are involved directly in expression of resistance to S. japonicum remains to be determined. However, this antigen produced by cloned DNA in expression vectors, or isolated from adult worms, is an obvious candidate to be tested for vaccination efficacy in mice.

Sj23, the target antigen in Schistosoma japonicum adult worms of an immunodiagnostic hybridoma antibody

Summary An IgG2a mouse hybridoma‐derived antibody (designated I.134) has been identified which binds to Schistosoma japonicum adult worms and which has immunodiagnostic potential (for detection of antibody) in schistosomiasis japonica in the Philippines. The target epitope of this hybridoma antibody is contained in a 23 000 molecular weight protein of adult worms as analysed by one‐dimensional sodium dodecyl sulphate‐polyacrylamide gel electrophoresis of immunoprecipitates and a gel overlay technique. This adult worm antigen has been labelled biosynthetically using35 S‐methionine as well as exogenously using lactoperoxidase‐catalysed radioiodination and the Bolton and Hunter reagent with intact worms. As anticipated, the low molecular weight protein antigen (designated Sj23) appears to be one of several major immunogenic proteins of worms which induce antibodies in infected Philippine patients.

Schistosoma japonicum: Infection characteristics in mice of various strains and a difference in the response to eggs

Abstract Female mice of 12 inbred strains were exposed to 20–25 cercariae of Schistosoma japonicum and infection status determined at day 40 by counting numbers of adult worms, eggs in faeces and eggs in a segment of liver. Most mouse strains appeared to be ‘permissive’ hosts although at least one strain (129/J) was shown to be relatively resistant in terms of day 40 adult worm numbers. In a radioisotopic lung assay for sensitivity to eggs, and developed as a rapid means of assessing granuloma formation, CBA/H mice were shown to differ from C57BL/6 mice in being non-responders. Histological examination of lungs of sensitized CBA/H and C57BL/6 mice injected intravenously with eggs established that granuloma formation was much more intense in C57BL/6 than CBA/H mice. Preliminary indications are that infected CBA/H mice are also low anti egg circumoval precipitin (COP) responders. Analysis of immune responses to isolated egg antigens in these two strains, and identification of the antigens of eggs to which such responses are directed in C57BL/6 mice, should provide insights into immunological disease processes (such as granulomatous inflammation) in this model system of japonicum schistosomiasis.

Examination of strategies for vaccination against parasitic infection or disease using mouse models.

There are currently no prophylactic or therapeutic vaccines against parasites of medical importance, the parasitic infections with major public health consequences being concentrated in tropical, less industrially developed countries. However, a limited number of living vaccines against economically important parasites is available in veterinary medicine, and vaccination efficacy of crude antigen preparations has been demonstrated time and again in laboratory models involving helminth, protozoan, and arthropod parasites (Clegg and Smith, 1978; Cox, 1978; Pery and Luffau, 1979; Murray et al., 1979; Mitchell, 1982a; Mitchell and Anders, 1982; Rickard and Williams, 1982).