authors request that the following correction be noted. Recent nucleotide sequence analysis has established that a C residue was omitted at position 628 of the Sj26 cDNA sequence presented in Fig. 2. The amended nucleotide sequence and the altered prediction of the COOH-terminal structure of Sj26 are given below. This correction does not otherwise affect the conclusions of the paper. ABSTRACT Mice of the inbred strain 129/J bred at this Institute (WEHI 129/J) are relatively resistant to chronic infection with the parasitic helminth Schistosomajaponicum. In contrast to more permissive mouse strains such as BALB/c, the WEHI 129/J mice are high responders to a Mr 26,000 adult worm antigen designated Sj26. Cloned cDNAs corresponding to Sj26 have been identified in a S. japonicum phage Xgtll amp3 expression library, and their nucleotide sequences have been deduced. The predicted amino acid sequence of the antigen specified by these cDNAs shows striking homology with class it isozymes of mammalian glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18). Extracts of adult worms contain glutathione S-transferase activity, and affinity chromatography of enzyme activity on glutathione columns leads to the purification of a Mr 26,000 molecule that comigrates with Sj26. Although vaccination studies in mice with a .3-galactosidase-Sj26 fusion protein from Escherichia coli are encouraging, more immunogenic preparations of the antigen are likely to be required to establish the utility of Sj26 as a model vaccine.
Attachment, the first phase of host identification by Schistosoma japonicum cercariae, can occur in 2 different ways. Cercariae clinging to the water surface simply swing around and transfer to the host skin. Free-swimming cercariae behave like S. mansoni: upon touching a substrate, they switch from tailward to forward movement, swim in an arc, and attach to it with the penetration organ. Neither type of attachment is influenced by chemical, thermal, or specific mechanical stimuli from the host. The second phase, remaining on the host, requires a solid hydrophobic surface and seems to depend only on the cercaria's ability to cling to it. This phase is not influenced by chemical or thermal stimuli. The third phase, creeping across the host surface, is independent of chemical and mechanical stimuli. Cercariae migrate in thermal gradients to a preferred temperature of 37 +/- 3 C and then attempt to penetrate. Penetration, the fourth phase, was evoked by human skin surface lipids. The free fatty acid (FA) fraction was identified as exclusively stimulating components. Saturated FA's were effective at chain lengths between 10 and 14 carbon atoms (pH 7.0), and unsaturated FA's were effective at longer chains and their activity increased with increasing number of double bonds. Dog skin surface components did not stimulate cercarial penetration, which can be attributed to the lack of free FA's. A temperature of 32-40 C also stimulated penetration responses, which might be the main stimulus in animal hosts, whose skin surfaces contain no or only a few free FA's. FA's and heat evoked a transformation of cercarial tegument simultaneous with penetration behavior, making the organisms osmotically sensitive. The host identification of S. japonicum cercariae is very nonspecific compared with the differentiated host recognition of S. mansoni.
Sex ratios of adult schistosomes in mice are almost invariably different from 1.0 and are biased towards males. The bias applies to wild rats infected with Schistosoma japonicum and trapped in an endemic area of the Philippines (male:female ratio = 1.7). It also applies to cercariae of snails collected in such areas and assessed by infection of laboratory mice using cercariae from individual snails (male:female ratio may approach 6.0). Experiments were designed to determine if duration of infection in the mammalian host was a factor that influenced the sex ratio of miracidia used for infecting snails and subsequently mice. BALB/c and C57BL/6 mice were infected with 100 cercariae of S. mansoni, and liver eggs harvested at early and late time points for infection of snails and production of cercariae. Two phenomena were demonstrated: firstly, a more pronounced male bias when eggs were harvested late compared with early in infection; secondly, a reduced apparent hatchability of eggs in BALB/c compared with C57BL/6 livers. The possibility is raised by the data that female miracidia within eggs of chronically infected individuals may be more prone to immune damage than male miracidia with important epidemiological consequences.
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 few 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.
Summary The radioisotopic assay for acute granulomatous hypersensitivity (AGH) to eggs of Schistosoma japonicum in mice sensitized with eggs in adjuvant has been examined in the high responder strain. C57BL/6. Responsiveness is expressed as the lung‐kidney ratio of radioactivity in mice challenged intravenously with eggs and injected with 123I‐iododeoxyuridine, Eggs vary in their AGH sensitizing and eliciting potency; eggs proven to be superior in the circumoval precipitation (COP) test for detection of human serum anti‐S. japonicum antibodies are superior in the C57BL/6 AGH assay. CBA/H are non responders and BALB/c are low to intermediate responders and are thus different from C57BL/6 mice. Short‐term infected CBA/H mice are low COP antibody responders relative to infected C57BL/6 and titres of IgM anti‐egg antibodies are low in the CRA/H strain as determined in a solid‐phase radioimmunoassay (RIA). Following egg sensitization. CBA/H mice are also lower responders than C57BL/6 mice in terms of antibodies with the specificity of a COP‐positive IgM hybridoma‐derived antibody, P.41, measured in a competitive RIA. No evidence has been obtained that alteration of the response to the target epitope of P.41 alters the responsiveness of C57BL/6 mice to S. japonicum eggs. Thus, large amounts of injected P.41 antibody do not alter lung AGH and induced anti‐idiotype responses to the P.41 protein do not influence AGH in egg‐sensitized C57BL/6 mice. However, immunization of C57BL/6 mice with another IgM anti‐schistosome hybridoma antibody, 1.39, results in partial inhibition of lung AGH responsiveness. The nature of the effect of 1.39 immunization on AGH to eggs remains unknown, but further analysis of the phenomenon may lead to novel approaches to the control of granulomatous inflammatory disease in high responders.
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