Passive transfer of resistance and the site of immune-dependent elimination of the challenge infection in rats vaccinated with highly irradiated cercarie of<i>Schistosoma mansoni</i>

The migration of isotopically labelled Schistosoma mansoni challenge cercariae was monitored, by means of squashed organ autoradiography, in naive Sprague-Dawley rats and rats protected with serum harvested from twice vaccinated donors. The majority of challenge larvae migrated from the skin to the lungs in both groups of rats, but a significantly increased number of larvae was retained in the lungs of serum recipients on day 8 post-challenge. An average of 25% of the challenge population succeeded in migrating to the livers of naive rats by day 14, compared to only 13% in passively protected animals; serum recipients were shown by perfusion on day 21 to be 73% immune. Histological examination of lung tissue harvested from naive rats challenged intravenously with lung-stage schistosomes revealed small foci composed of mononuclear cells that sometimes enclosed larvae; these worms are likely to be lost due to innate resistance. In the lungs of serum-protected rats, many challenge larvae were seen to be surrounded by extensive eosinophil-enriched inflammatory foci; parasite remnants were also observed within such reactions. Ultrastructural examination of worms recovered from the lungs of passively protected animals revealed muscle disruption and internal vacuolation, although the tegument remained intact. It is proposed that challenge attrition in serum-protected rats occurs essentially in the lungs and involves larval immobilization and subsequent death, perhaps mediated by cellular mechanisms.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Schistosoma mansoni: migration and attrition of challenge parasites in naive rats and rats protected with vaccine serum

Ward¹,

McLaren²

1989

“…The identification of the schistosomula antigenic targets of protective antibodies produced by unattenuatted S. mansoni-infections of non-permissive (rats and rabbits) hosts, that can transfer protection to permissive hosts such as the mouse, warrants investigation. Antibodies present in the sera of mice, rats and rabbits vaccinated with irradiated larvae have been shown to constitute at least one of the effector mechanisms responsible for protection in passive transfer experiments, with respect to both S. mansoni (Ford et al 1984, Mangold & Dean 1986 and S. japonicum (Moloney & Webbe, 1990). In this study also it was shown that the IgG fraction of Protein A-fractionated IRS conferred protection against schistosome challenge, but the non-binding fraction failed to do so.…”

Section: Discussionmentioning

confidence: 52%

Protection of mice against Schistosoma mansoni infection by passive transfer of sera from infected rabbits

Fallon

Fookes

Doenhoff

1996

Sera from rabbits infected with unattenuated Schistosoma mansoni cercariae conferred significant levels of protection against S. mansoni challenge (P < 0.001) after passive transfer to mice. Infected rabbit sera were only effective in conferring protection when transferred during the first week of infection, and were not effective when administered against liver-stage worms. Immunoglobulins isolated from the infected rabbit sera with Protein A-Sepharose were shown to be responsible for the transfer of protection to mice. Immunofluorescence studies demonstrated that the sera were more reactive against the surface of three hour-old mechanically transformed schistosomula than against the surfaces of lung-stage schistosomula. The sera from infected rabbits reacted polyspecifically against antigens in cercaria, schistosomula, and the worm and egg stages of the S. mansoni life-cycle. The host parasite relationship of S. mansoni in the rabbit is discussed.

“…Anti-r140 antibodies were found to react uniquely with natural antigen Sm25 in worm extracts using WIB, yet failed to induce significant protection in either animal model. This was an unexpected finding in the rat model, where parasite killing is primarily via antibody-mediated mechanisms (Phillips et al 1978, Mangold & Knopf 1981, Ford et al 1984, Capron et al 1987. Antibodies have also been shown to play a significant role in mice protected with repeated exposures to irradiated cercarial vaccines while a single exposure results in predominantly Th-1-driven protective cellular responses (Caulada-Benedetti et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni

Suri

Goldberg

Madikizela

et al. 1997

To investigate the role of tegumental glycoprotein Sm25 in protective immunity against schistosomiasis, codons 43-182 of its gene (GP22) were amplified by PCR and cloned in the pET 15b bacterial expression system. Recombinant protein r140 was inducibly expressed in the presence of rifampicin and purified by Ni-affinity chromatography. In different vaccination trials, Balb/c mice and Fischer rats repeatedly immunized with r140 in combination with one of several adjuvants (alum, cholera toxin or complexed into proteosomes) produced high titre anti-r140 responses. These antibodies detected an N-glycanase sensitive. 25 kDa antigen in a detergent solubilized worm fraction using Western immunoblotting. The choice of adjuvant affected the isotype distribution of the specific anti-r140 antibodies. Despite the presence of high antibody titres and isotypes which have been shown to correlate with protective immunity, protection against subsequent cercarial challenge was not observed. In addition, no appreciable effects on worm sex ratios or liver egg yields were detected in mice. Studies involving biotin labelling of membrane proteins in live worms showed that the majority of anti-r140 reactive molecules present in adult schistosomes are biotinylated after permeabilization of the parasite surface. Several possibilities to account for the lack of protective immunity are analysed.