title: Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.
abstract: The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.
authors.affiliation: Queensland Tropical Health Alliance and School of Public Health and Tropical Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Pearson
authors.forename: Darren A
authors.initials: DA
authors.lastname: Pickering
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
authors.forename: Leon
authors.initials: L
authors.lastname: Tribolet
authors.forename: Annette M
authors.initials: AM
authors.lastname: Dougall
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D057055:Aspartic Acid Proteases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D059470:Tetraspanins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D059470:Tetraspanins; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D057055:Aspartic Acid Proteases