Molecular cloning and enzymatic expression of the 28-kDa glutathione S-transferase of Schistosoma japonicum: evidence for sequence variation but lack of consistent vaccine efficacy in the murine host.
Glutathione S-transferases (GSTs) have long been regarded as attractive vaccine (and drug) targets in schistosomes due to their suspected role in detoxification processes. Indeed, the 28-kDa GST of Schistosoma mansoni (SmGST28) has proven efficacy as an antigen for protective immunity reducing worm burden, female fecundity and egg viability. In contrast, the vaccinating effects of the bacterial expressed homologue of Philippine S. japonicum (SjpGST28) have proved disappointing, possibly because this recombinant form was an incomplete sequence, lacking five N-terminal amino acids which may have affected its vaccination efficacy. Here we describe the cloning and functional enzymatic expression of a complete cDNA encoding SjpGST28. We report also on the immunogenicity and vaccine efficacy of this molecule as a purified recombinant protein and as a DNA plasmid vaccine in the murine model. We further describe the cloning of several complete cDNAs encoding the Chinese homologue of SjpGST28 and the identification of 3 SjcGST28 sequence variants which are probably encoded by distinct alleles.
Scott
J C
JC
Molecular Parasitology Unit, Australian Centre for International and Tropical Health and Nutrition, The University of Queensland, Post Office Royal Brisbane Hospital, Herston, Queensland 4029, Brisbane, Australia.
McManus
D P
DP
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D012549:Schistosoma japonicum / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D014612:Vaccines; D005982:Glutathione Transferase