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PubMed1988

Serum from CBA/Ca mice vaccinated with irradiated cercariae of Schistosoma mansoni protects naive recipients through the recruitment of cutaneous effector cells.

Passive transfer experiments showed that 76% of the resistance induced in CBA/Ca mice by exposure to radiation-attenuated cercariae of Schistosoma mansoni could be transferred to naive recipients by administration of donor serum. The level of protection achieved depended on the volume of serum administered and immunity was demonstrated most consistently with serum harvested from thrice vaccinated donors. The serum was twice as effective when given to the recipients at the time of cercarial challenge as compared to administration 5 days after challenge, a result which indicates that serum-dependent challenge elimination is probably accomplished in the cutaneous tissues. This view was confirmed by the observation that passive protection could be ablated by administration of a monoclonal antibody which we have shown elsewhere to deplete the cutaneous inflammatory reaction to cercarial penetration. Histopathological studies revealed that vaccine serum induced subdermal inflammatory reactions in challenged recipient mice which were identical both in induration and kinetics to those seen in conventionally vaccinated individuals; on days 4 and 5 post-challenge, the reactions comprised 60% mononuclear cells and 40% eosinophils. Challenge larvae, which had transformed from skin-stage to lung-stage parasites, became trapped within such reactions and eventually showed generalized vacuolation consistent with the onset of damage. Some foci were seen to contain degenerated leucocytes, free eosinophil granules and debris which is thought to represent the remnants of dead parasites. Small focal reactions were identified on occasion in naive challenged mice and in recipients of normal mouse serum, but these reactions comprised predominantly mononuclear cells and were rarely seen to encompass challenge parasites. These data show that serum-transferred resistance in the vaccinated CBA/Ca mouse model involves the induction of a cutaneous inflammatory response in the recipients.

Animals↗
PubMed1990

Schistosoma mansoni: analysis of the humoral and cellular basis of resistance in guinea-pigs vaccinated with radiation-attenuated cercariae.

This study addresses the humoral and cellular basis of specific acquired immunity in the guinea-pig irradiated vaccine model of schistosomiasis mansoni. Rodents vaccinated with 500 gamma-irradiated cercariae and then splenectomized 4.5 weeks later showed a 33% reduction in resistance to challenge as compared to vaccinated animals or vaccinated/sham splenectomized controls. Serum harvested from once vaccinated individuals conferred modest levels of resistance upon naive recipients in some experiments, but transfer was not achieved consistently. Serum from vaccinated and thrice boosted rodents (Vbbb) routinely transferred around 45% immunity, however, provided it was given in 4 ml aliquots on day 9 post-challenge; Vbbb serum thus transferred 50% of donor immunity. Interestingly, multiple doses of this protective serum given on and either side of day 9 did not enhance the protection achieved with a single 4 ml aliquot. Neither peripheral lymph node cells nor splenocytes from the polyvaccinated serum donors were able to transfer resistance to recipient guinea-pigs and they failed to augment the protection achieved with Vbbb serum. Foot-pad testing revealed no correlation between delayed hypersensitivity responses and immunity to challenge in vaccinated guinea-pigs. Although polyvaccine guinea-pig serum successfully protected homologous recipients, it failed to protect mice when administered either at the time of challenge (the optimal schedule for transfer of polyvaccine mouse serum), or around day 9 (the optimal schedule for guinea-pigs). Similarly, guinea-pigs could not be protected with polyvaccine rat serum that conferred 75% resistance upon naive recipient rats.

Animals↗
PubMed1990

Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae.

Sera from rabbits, rats and mice multiply-vaccinated with attenuated cercariae of Schistosoma japonicum conferred high levels of resistance against challenge to naive recipient mice (up to 97, 64 and 60% respectively). Vaccinated rabbit and rat sera were given before challenge and vaccinated mouse serum 5 days after challenge. To show that the protective factors in these sera were antibodies, vaccinated rabbit and mouse sera were fractionated by protein A-Sepharose and the fractions precipitated by 50% ammonium sulphate. The protein A-Sepharose binding or non-binding fractions in vaccinated rabbit serum transferred approximately equal levels of significant resistance to mice, suggesting that both the IgG and non-IgG components of vaccinated rabbit serum are protective. The major part of the protective activity in vaccinated mouse serum was transferred to recipients by the protein A-Sepharose binding fraction, i.e. the IgG antibodies. Heat inactivation of sera at 56 degrees C for 3 h affected the protective capacity of vaccinated rat sera, but not that of vaccinated rabbit or mouse sera.

Animals↗
PubMed1986

Migration of the schistosomula of Schistosoma mansoni in mice vaccinated with radiation-attenuated cercariae, and normal mice: an attempt to identify the timing and site of parasite death.

The migration of the schistosomula of Schistosoma mansoni labelled with [75Se]methionine, has been followed from the skin to the hepatic portal system. Parasites were detected in all mouse tissues by compressed organ autoradiography. Two separate experiments were performed to track parasites in normal mice, and in mice previously vaccinated with irradiated cercariae. In normal mice, the profile of numbers of autoradiographic foci detected in the skin, lungs, systemic and splanchnic organs was described with time post-infection. The distribution of parasites to systemic organs, following exit from the lungs, paralleled the fractional distribution of cardiac output. Accumulation of schistosomula in the hepatic portal system was complete by day 21 post-infection. Only 2-3 passes of parasites around the vascular system would be required to produce the hepatic portal population. No significant decline in total foci was detected in the first 12 days post-infection. The majority of parasite elimination appeared to occur in the lungs as late as day 21, with lesser proportions in the systemic organs and skin infection site. The pattern of migration in vaccinated mice was similar to that in normal animals. One difference observed was the longer duration of stay in the skin; however, the majority of parasites eventually reached the lungs. The systemic phase of migration occurred on a reduced scale, as did accumulation of parasites in the hepatic portal system. The decline in total foci in vaccinated mice commenced approximately 7 days earlier than in normal mice and proceeded to a lower end-point. Again the majority of parasite elimination appeared to occur in the lungs with lesser proportions in the systemic organs and skin infection site. It is suggested that resistance to reinfection in vaccinated mice has two additive components which combine to retard the migration of schistosomula within the vasculature, preventing them from reaching the hepatic protal system.

Animals↗
PubMed1991

Effects of temperature and host density on the snail-finding capacity of cercariae of Echinostoma caproni (Digenea: Echinostomatidae).

The effect of temperature (19-36 degrees C) and snail host density (0.014-10 snails/l) on the snail-finding capacity of Echinostoma caproni cercariae is described. The initial swimming speed increased whereas the length of the infective period decreased with increasing temperature. The combined effect resulted in the E. caproni cercarial snail-finding capacity being temperature independent in the range 19 to 36 degrees C at a snail density of 0.014 snails/l. A moderate temperature dependency was, however, seen at a lower snail density. The cercarial snail-finding capacity was snail-host density dependent in the density range 0.014 to 1 snail/l. The findings from this study show that a relatively low and biologically realistic snail host density must be used in experimental studies if realistic estimates of the dynamics of cercarial transmission are to be obtained.

Analysis of Variance↗
PubMed1996

Protective immunity to Schistosoma mansoni induced in the olive baboon Papio anubis by the irradiated cercaria vaccine.

The radiation-attenuated schistosome vaccine induces a high level of protective immunity in rodents. In order to assess its potential relevance to man, we have tested its efficacy in the non-human primate Papio anubis. A vaccination regime consisting of 3 exposures of approximately 9000 cercariae irradiated with 30 or 60 krad. of gamma radiation induced > 50% protection to a challenge with normal larvae. A lower attenuating dose of 20 krad., optimal for vaccination of mice, was less effective. All vaccination regimes elicited a population of PBMC which proliferated in vitro in response to antigen. These responses peaked after the third exposure but were significantly lower after challenge. They revealed relatively little cross-reactivity with adult Schistosoma haematobium antigens and provided some evidence for stage-specific antigens. Circulating IgM reactive with adult S. mansoni antigen was detected after the second vaccination but levels remained low throughout. In contrast, IgG levels were boosted by successive vaccinations, although they showed a tendency to decline from 14 days after each exposure. There also appeared to be a lag of about 14 days after challenge before levels began to rise. Thus, both proliferation and antibody data suggest a lower responsiveness after challenge which may reflect either the reduced antigenic load or immunogenicity of normal, compared to vaccinating larvae. The data indicate that the attenuated schistosome vaccine is capable of inducing protection in a highly permissive primate host, with the implication that the mechanisms involved may also be relevant to man.

Animals↗
PubMed1983

The relationship between the age of Schistosoma mansoni cercariae and their ability to penetrate and infect the mammalian host.

The ability of the cercariae of Schistosoma mansoni to penetrate the tails of mice was shown to remain constant throughout their lives. However, their capacity to establish themselves and then reach maturity decreased as they aged. The abdominal route of penetration produced consistently higher maturation rates than the tail route. Significantly different maturation rates were obtained by modifying the standard tail infection technique. Evidence is presented that age-related mortality of schistosomula occurs within 24 h of penetration and may be associated with the exhaustion of energy reserves during the penetration of the stratum corneum. The relationship of this age-related mortality to 'mass mortality' is discussed.

Age Factors↗
PubMed2002

Antibodies induced in mice by a DNA-construct coding for the elastase of Schistosoma mansoni recognize the enzyme in secretions and preacetabular glands of cercariae.

A DNA-construct coding for the elastase of the parasite Schistosoma mansoni was prepared from adult S. mansoni worm RNA which was reverse transcribed into cDNA. The gene coding for the elastase was amplified using primers specific for the sequence of cercarial elastase and was cloned into a mammalian expression vector. Expression of the elastase gene at the transcriptional level was achieved for the first time in transfected mammalian cells (COS-7) and was also successful in muscle tissue of mice injected with the DNA-construct. These mice developed antibodies recognizing in Western blots the elastase from cercarial secretions. Also, these antibodies reacted in immunofluorescence tests with the preacetabular glands of cercariae, i.e. the site of origin for elastase. Thus, the DNA-construct induced the expression of elastase in mice and formation of antibodies that recognized the native antigen.

Animals↗
PubMed2003

Delayed tail loss during the invasion of human skin by schistosome cercariae.

Schistosomiasis is initiated when cercarial larvae invade human skin. Contrary to long-held assumptions, most cercariae of Schistosoma mansoni do not shed their propulsive tails as they penetrate. Scanning electron microscopy studies and infection experiments with entire human skin and differentiated, stratum corneum-like, human keratinocyte cultures, have shown that most cercarial tails enter the skin along with their bodies. We propose that this behaviour is an adaptive trait linked with concomitant immunity.

Animals↗
PubMed2003

An ultrastructural study of reproduction in the parthenogenetic metacercariae of Cercaria margaritensis Ching, 1982 (Digenea: Gymnophallidae).

The parthenogenetic metacercarial stages of the gymnophallid trematode Cercaria margaritensis are found in the extrapallial cavity of the subtidal prosobranch mollusc Margarites helicinus. The primary metacercariae (M1) produce second-generation metacercariae (M2) which become independent and give rise to M3 metacercariae which are infective to the definitive host, the common eider (Somateria mollissima). This study used transmission electron microscopy to follow the development of M2 inside M1 organisms and M3 inside M2 organisms. The process is similar in both cases with embryos developing from individual cells from the parent body walls. In each case the brood sac was divided into brood chambers by multilaminated cells and both M2 and M3 embryos developed inside embryonic membranes that originated from specialized blastomeres. The tegument of M2 and M3 embryos developed in a similar manner underneath the embryonic membrane. Both the multilaminated cells and the embryonic membranes possessed features that indicated that they are involved in transport of nutrients. It is suggested that the continuous nature of M2 and M3 embryo development may well be similar to that postulated for ancestral digeneans.

Animals↗
PubMed2004

An ultrastructural study of excretory system development in the cercariae of Prosorhynchoides gracilescens (Rudolphi, 1819) and Prosorhynchus squamatus Odhner, 1905 (Digenea, Bucephalidae).

The ultrastructure of the developing excretory system of Prosorhynchoides gracilescens and Prosorhynchus squamatus cercariae is described. The development pattern was similar in both species. In early embryos the two main collecting tubes were composed of a layer of cells which were wrapped around the lumen. Later, the tubes fused and the excretory epithelium of the fusion zone and that of the lateral caudal ducts became a syncytium. The collecting tubes in the cercarial body retained their cellular organization. As the tails grew, additional excretory pores were formed in the tail stem where thickened portions of the caudal duct epithelium contacted the surface tegument. Following this, the distal portions of the lateral caudal ducts lost contact with the primary excretory pores and progressively degenerated. Excretory atrium development started with differentiation of secretory active cytons peripheral to the fusion zone. These cells gave rise to cytoplasmic extensions that penetrated the fusion zone wall to eventually form a continuous cytoplasmic layer. This layer eventually replaced some of the fusion zone excretory epithelium and became the lining of the excretory atrium. The anterior end of the fusion zone differentiated into an excretory bladder and a short posterior portion gave rise to the caudal vesicle.

Animals↗
PubMed2005

Mapping fucosylated epitopes on glycoproteins and glycolipids of Schistosoma mansoni cercariae, adult worms and eggs.

The developmental expression of the antigenic fucosylated glycan motifs Fucalpha1-3GalNAcbeta1-4GlcNAc (F-LDN), Fucalpha1-3GalNAcbeta1-4(Fucalpha1-3)GlcNAc (F-LDN-F), GalNAcbeta1-4(Fucalpha1-3)GlcNAc (LDN-F), Galbeta1-4(Fucalpha1-3)GlcNAc (Lewis X), and GalNAcbeta1-4(Fucalpha1-2Fucalpha1-3)GlcNAc (LDN-DF) in Schistosoma mansoni cercariae, adult worms and eggs, was surveyed using previously defined anti-carbohydrate monoclonal antibodies (mAbs). Lewis X was found both on glycolipids and glycoproteins, yet with completely different expression patterns during the life-cycle: on glycolipids, Lewis X was mainly found in the cercarial stage, while protein-conjugated Lewis X was mainly present in the egg stage. Also protein-conjugated LDN-F and LDN-DF were most highly expressed in the egg-stage. On glycolipids LDN-DF was found in all three examined stages, whereas LDN-F containing glycolipids were restricted to adult worms and eggs. The motifs F-LDN and F-LDN-F were found both on glycoproteins and glycolipids of the cercarial and egg stage, while in the adult stage, they appeared to occur predominantly on glycolipids. Immunofluorescence assays (IFA) showed that these F-LDN and F-LDN-F containing glycolipids were localized in a yet undefined duct or excretory system of adult worms. Murine infection serum showed major reactivity with this adult worm duct-system, which could be fully inhibited by pre-incubation with keyhole limpet haemocyanin (KLH). Clearly, the use of defined mAbs provides a quick and convenient way to map expression profiles of carbohydrate epitopes.

Amino Acid Motifs↗
PubMed1982

Partial purification and characterization of an inhibitor from newborn-rat epidermis with activity against the proteinase of Schistosoma mansoni cercariae.

The penetration of cercariae through the skin initiates infection of the host with the human trematode parasite Schistosoma mansoni. Many larvae fail to migrate into the living epidermal cell layer. In order to determine if chemical as well as mechanical barriers to cercarial skin penetration exist, inhibitory activity of epidermal cell extracts against the proteinase obtained from cercarial secretions was assayed. An inhibitor was purified 50-fold by gel filtration on Sephadex G 75 and cation exchange chromatography at pH 5.8 and 4.9. The inhibitor has a relative molecular mass (Mr) of approx. 40 000-53 000. Oxidation of the inhibitor with N-chlorosuccinimide eliminated its inhibitory activity and thus indicated a critical methionine residue. The inhibitor was active against a wide spectrum of serine proteinases: porcine pancreatic elastase, human granulocyte elastase, bovine trypsin, and bovine alpha-chymotrypsin. However, no inhibition was detected against papain or clostridial collagenase. The inhibitor did not cross react with antiserum to human or rat serum alpha 1-proteinase inhibitor.

Animals↗
PubMed1996

Kinetics and mechanism of effector focus formation in the lungs of mice vaccinated with irradiated cercariae of Schistosoma mansoni.

The sequence of events involved in effector focus formation around challenge schistosomula in the lungs of mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni has been characterized following intravenous administration of lung stage larvae. Histopathological analysis of the lungs of vaccinated animals revealed that infiltrating cells were present around larvae within 24 h. The main increment in cell recruitment occurred between 2 and 4 days, with foci reaching maximal diameter on day 8. No additional infiltration of the airways was detected by bronchoalveolar sampling before day 4 when the maximum number of cells, predominantly lymphocytes, was recovered. In contrast, responses in challenge control animals were relatively slight prior to day 12. IFN gamma was the major cytokine in airway cultures from vaccinated mice, the greatest increment in production coinciding with peak cell recruitment. A similar pattern of IFN gamma mRNA expression was observed in whole lung extracts, highlighting the dominance of Th1 responses in the effector mechanism. The slow start to focus formation may be due to the need for antigen, released by the intravascular parasite, to be translocated across the endothelium, processed by accessory cells and presented to the helper T cells which orchestrate the effector mechanism. The delay is of the same order as the period of development which the parasite must undergo in the lung, to facilitate further migration. This similarity in the timing may explain why some larvae are able to avoid the consequences of the pulmonary effector response.

Animals↗
PubMed1984

Biology and behaviour of the cercariae of a Sanguinicola sp. in the river Cilloruelo (Salamanca, Spain).

In the light of the hydrodynamic characteristics of the river Cilloruelo (province of Salamanca, Spain) and the results on the shedding of lophocercariae of a Sanguinicola sp. by naturally infected Ancylus fluviatilis, a discussion is made of the influence of different temperatures on shedding and survival of the cercariae. Comments are also made concerning the most likely periods and zones of the river for infection of the definitive host.

Animals↗
PubMed1986

[Shedding pattern of Schistosoma japonicum cercariae from mainland China by Oncomelania hupensis].

The release of Schistosoma japonicum cercariae from the People's Republic of China shedded by Oncomelania hupensis was observed hourly under laboratory conditions: LD 9 - 15, T degrees = 25 degrees C. Daily periodicity of emergence was recognized during the light period. Peaks emergence occurs between 2 and 5 p.m. Results are compared with other geographical strains of S. japonicum.

Animals↗