Characterization of a novel vaccine candidate and serine proteinase inhibitor from Schistosoma japonicum (Sj serpin).
Serine proteinase inhibitors (serpins) represent an important superfamily of endogenous inhibitors that regulate proteolytic events active in a variety of physiological functions. Immunological screening of a Schistosoma japonicum adult worm cDNA expression library with sera of Microtus fortis, a naturally resistant vertebrate host, has identified one clone that encoded for a sequence homologous to those of the serpin superfamily. The full-length sequence encoding S. japonicum serpin (Sj serpin) was amplified from adult worm cDNA by using 5'-RACE-PCR and subsequently cloned into the prokaryotic expression vector pET28c. The full-length Sj serpin fusion-protein with his-tag was expressed in E. coli, purified by affinity chromatography and used to immunize New Zealand white rabbits. Sj serpin is located on the tegument in S. japonicum adult worms. C57BL/6 mice immunized with Sj serpin induced the production of high levels of specific IgE and IgG1 subclass antibodies as well as a marked IL-4 response. Lymphocyte surface marker analysis revealed proliferation of CD19 expressing B cells, indicating a predominant Th2-type response to Sj serpin. Immunized mice developed moderate protection against infection of S. japonicum as demonstrated by a 36 and 39% reduction in the recovery of adult worms and eggs, respectively. These data suggested a role for Sj serpin as a vaccine candidate or as a novel target for anti-schistosome drugs.
Yan
Yutao
Y
Emory University, 615 Michael ST, Atlanta, GA 30322, USA. yyan@emory.edu
Liu
Shuxian
S
Song
Guangcheng
G
Xu
Yixin
Y
Dissous
Colette
C
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D001483:Base Sequence; D003001:Cloning, Molecular; D006224:Cricetinae; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D007114:Immunization / Q000662:veterinary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000662:veterinary; D018510:RNA, Helminth / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D012549:Schistosoma japonicum / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D016415:Sequence Alignment; D015843:Serpins / Q000235:genetics / Q000276:immunology*
D000909:Antibodies, Helminth; D016207:Cytokines; D018510:RNA, Helminth; D011994:Recombinant Proteins; D015843:Serpins