Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella.
A vector has been constructed to allow genetic fusions of guest antigens via a hinge domain to the C terminus of the highly immunogenic C fragment of tetanus toxin. A fusion has been constructed with the gene encoding the protective 28-kDa glutathione S-transferase (EC 2.5.1.18) from Schistosoma mansoni. The recombinant vector has been electroporated into the nonvirulent Salmonella typhimurium aroA live vaccine strain SL3261. The corresponding chimeric protein is stably expressed in a soluble form in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice immunized intravenously with a single dose of the live recombinant bacteria elicit antibodies to both fragment C and glutathione S-transferase as detected by enzyme-linked immunosorbent assays. Furthermore, all of the mice were solidly protected when challenged with lethal doses of either tetanus toxin or the virulent Salmonella typhimurium strain C5. Mice have also elicited antibodies to fragment C and glutathione S-transferase after oral immunization. It may be that a live trivalent vaccine against typhoid, tetanus, and schistosomiasis is feasible.
Khan
C M
CM
Department of Pathology, University of Cambridge, United Kingdom.
Villarreal-Ramos
B
B
Pierce
R J
RJ
Riveau
G
G
Demarco de Hormaeche
R
R
McNeill
H
H
Ali
T
T
Fairweather
N
N
Chatfield
S
S
Capron
A
A
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000947:Antigens, Helminth / Q000235:genetics*; D001428:Bacterial Vaccines; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology*; D015801:Helminth Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012475:Salmonella / Q000276:immunology*; D012550:Schistosoma mansoni / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D013744:Tetanus Toxin / Q000235:genetics* / Q000276:immunology; D014613:Vaccines, Attenuated
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D001428:Bacterial Vaccines; D017931:DNA Primers; D015801:Helminth Proteins; C052358:P28 antigen, Schistosoma; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D014613:Vaccines, Attenuated; D005982:Glutathione Transferase