Sm14 of Schistosoma mansoni in fusion with tetanus toxin fragment C induces immunoprotection against tetanus and schistosomiasis in mice.
We have constructed vectors that permit the expression in Escherichia coli of Schistosoma mansoni fatty acid-binding protein 14 (Sm14) in fusion with the nontoxic, but highly immunogenic, tetanus toxin fragment C (TTFC). The recombinant six-His-tagged proteins were purified by nickel affinity chromatography and used in immunization and challenge assays. Animals inoculated with TTFC in fusion with or coadministered with Sm14 showed high levels of tetanus toxin antibodies, while animals inoculated with Sm14 in fusion with or coadministered with TTFC showed high levels of Sm14 antibodies. In both cases, there were no changes in the type of immune response (Th2) obtained with the fusion proteins compared to those obtained with the nonfused proteins. Mice immunized with the recombinant proteins (TTFC in fusion with or coadministered with Sm14) survived the challenge with tetanus toxin and did not show any symptoms of the disease. Control animals inoculated with either phosphate-buffered saline (PBS) or Sm14 died with severe symptoms of tetanus after 24 h. Mice immunized with the recombinant proteins (Sm14 in fusion with or coadministered with TTFC) showed a 50% reduction in worm burden when they were challenged with S. mansoni cercariae, while control animals inoculated with either PBS or TTFC were not protected. The results show that the expression of other antigens in fusion at the carboxy terminus of TTFC is feasible for the development of a multivalent recombinant vaccine.
Abreu
Patrícia A E
PA
Centro de Biotecnologia, Instituto Butantan, Universidade de São Paulo, Brazil.
Miyasato
Patrícia A
PA
Vilar
Mônica M
MM
Dias
Waldely O
WO
Ho
Paulo L
PL
Tendler
Míriam
M
Nascimento
Ana L T O
AL
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000909:Antibodies, Helminth / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D050612:Fatty Acid Transport Proteins; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D015996:Survival Rate; D013742:Tetanus / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000633:toxicity; D014611:Vaccination; D014612:Vaccines / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D000909:Antibodies, Helminth; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D015801:Helminth Proteins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D014612:Vaccines; D014614:Vaccines, Synthetic; C040635:tetanus toxin fragment C; C068709:SM14 protein, Schistosoma mansoni