Molecular cloning of components of protective antigenic preparations has suggested that related parasite fatty acid-binding proteins could form the basis of the protective immune crossreactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. Molecular models of the two parasite proteins showed that both molecules adopt the same basic three-dimensional structure, consisting of a barrel-shaped molecule formed by 10 antiparallel (8-pleated strands joined by short loops, and revealed the likely presence of crossreactive, discontinuous epitopes principally derived from amino acids in the C-terminal portions of the molecules. A recombinant form of the S. mansoni antigen, rSml4, protected outbred Swiss mice by up to 67% against challenge with S. mansoni cercariae in the absence of adjuvant and without provoking any observable autoimmune response. The same antigen also provided complete protection against challenge with F. hepatica metacercariae in the same animal model. The results suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni, of veterinary and human importance, respectively. Schistosomiasis, caused principally by Schistosoma mansoni, S. haematobium, and S. japonicum, afflicts some 200 million individuals in tropical regions of the world. Fascioliasis caused by Fasciola hepatica is an economically important disease of cattle and sheep in Europe, the Americas, Australia, and New Zealand. There are no vaccines against Schistosoma or Fasciola species; however, there is evidence for protective immune crossreactivity between S. mansoni and F. hepatica. Hillyer and coworkers (1-3) have isolated a low molecular weight F. hepatica fraction that protects against both S. mansoni and F. hepatica infections. A component of this fraction is an antigen with homology to mammalian fatty acid-binding proteins that is termed Fhl5 (4). A similar antigen, Sm14, was cloned from S. mansoni following studies of a protective saline extract of adult worms, SE (5). These results suggested that the pair of similar parasite proteins could mediate immune crossreaction and represent the basis of a subunit vaccine effective against both species. We have investigated the molecular relationship of Fhl5, Sml4, and mammalian fatty acid-binding proteins (FABPs) (6) (9), and rat intestine (10) were obtained directly from the Brookhaven Protein Data Bank (accession codes 2HMB, 1ALB, and 2IFB, respectively). Sequences of known crystal structure were aligned by leastsquares superposition of the molecules using C' coordinates alone, and the remaining sequences were subsequently incorporated into the alignment by the method of Barton and Sternberg (11) as implemented in the AMPS package.For the construction of the Sm14 model, the backbone of the 10 (3-strands and three a-helices was based on that of 1ALB. (3-Turn types were determined on the basis of the position of glycine and/or asparagine and aspartic residues within ...
Previous studies carried out with Sm14 in experimental vaccination against Schistosoma mansoni or Fasciola hepatica infections were performed with recombinant Sm14 (rSm14) produced in Escherichia coli by the pGEMEX system (Promega). The rSm14 was expressed as a 40 kDa fusion protein with the major bacteriophage T7 capsid protein. Vaccination experiments with this rSm14 in animal models resulted in consistent high protective activity against S. mansoni cercariae challenge and enabled rSm14 to be included among the vaccine antigens endorsed by the World Health Organization for phase I/II clinical trials. Since the preparation of pGEMEX based rSm14 is time consuming and results in low yield for large scale production, we have tested other E. coli expression systems which would be more suitable for scale up and downstream processing. We expressed two different 6XHis-tagged Sm14 fusion proteins in a T7 promoter based plasmids. The 6XHis-tag fusions allowed rapid purification of the recombinant proteins through a Ni+2-charged resin. The resulted recombinant 18 and 16 kDa proteins were recognized by anti-Sm14 antibodies and also by antiserum against adult S. mansoni soluble secreted/excreted proteins in Western-Blot. Both proteins were also protective against S. mansoni cercariae infection to the same extent as the rSm14 expressed by the pGEMEX system
Os conceitos evolucionistas começaram a se fundamentar a partir de Descartes, Buffon, Lamarck e Darwin e ao mesmo tempo despertaram as contradições das doutrinas criacionistas. A credibilidade do evolucionismo por faixa etária dos alunos de graduação da Universidade Severino Sombra (USS), nas diferentes áreas do saber foi o objeto deste trabalho. A população discente se concentrou na faixa etária entre 20 a 24 anos em que predomina o acreditar em ideias evolucionistas, não se podendo avaliar se estes posicionamentos independem da divulgação ou do ensino do criacionismo introduzido há algum tempo nas escolas públicas de alguns estados brasileiros. Pode-se inferir, a partir deste estudo, um grande desconhecimento sobre a teoria científica evolucionista entre os discentes dos cursos superiores pesquisados na USS.
Os conceitos evolucionistas começaram a se fundamentar a partir de Descartes, Buffon, Lamarck e Darwin e ao mesmo tempo despertaram as contradições das doutrinas criacionistas. A credibilidade do evolucionismo por faixa etária dos alunos de graduação da Universidade Severino Sombra (USS), nas diferentes áreas do saber foi o objeto deste trabalho. A população discente se concentrou na faixa etária entre 20 a 24 anos em que predomina o acreditar em ideias evolucionistas, não se podendo avaliar se estes posicionamentos independem da divulgação ou do ensino do criacionismo introduzido há algum tempo nas escolas públicas de alguns estados brasileiros. Pode-se inferir, a partir deste estudo, um grande desconhecimento sobre a teoria científica evolucionista entre os discentes dos cursos superiores pesquisados na USS.
Os conceitos evolucionistas começaram a se fundamentar a partir de Descartes, Buffon, Lamarck e Darwin e ao mesmo tempo despertaram as contradições das doutrinas criacionistas. A credibilidade do evolucionismo por faixa etária dos alunos de graduação da Universidade Severino Sombra (USS), nas diferentes áreas do saber foi o objeto deste trabalho. A população discente se concentrou na faixa etária entre 20 a 24 anos em que predomina o acreditar em ideias evolucionistas, não se podendo avaliar se estes posicionamentos independem da divulgação ou do ensino do criacionismo introduzido há algum tempo nas escolas públicas de alguns estados brasileiros. Pode-se inferir, a partir deste estudo, um grande desconhecimento sobre a teoria científica evolucionista entre os discentes dos cursos superiores pesquisados na USS.
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