title: Heterologous expression of the cuticular-glutathione peroxidase of lymphatic filariae in an attenuated vaccine strain of Salmonella typhimurium abrogates H-2 restriction of specific antibody responses.
abstract: The major soluble cuticular glycoprotein of lymphatic filariae, gp29, has been expressed in the Salmonella typhimurium aroA aroD live vaccine strain BRD509. Two distinct constructs were generated: a) pgp29, in which gp29 was expressed directly via the inducible promoter nirB, or b) pTetC-gp29, in which it was expressed as a C-terminal fusion to the non-toxic immunogenic fragment C of tetanus toxin, again under the control of nirB. In both cases, plasmid stability in vivo was demonstrated by recovery of recombinant bacteria from livers and spleens of mice immunized via the intravenous route. Negligible gp29-specific antibodies were detected in animals immunized with bacteria expressing the fragment C fusion protein, but bacteria expressing the non-fused protein resulted in gp29-specific antibody production in a proportion of animals immunized. Notably, a number of BALB/c and B10.D2/n (i.e. mice of the H-2d haplotype) responded, in contrast to previously documented nonresponsiveness during infection, or immunization with parasite extracts. Presentation of gp29 by live attenuated S. typhimurium resulted in a broad spectrum of antigen-specific IgG isotypes.
authors.affiliation: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Chacón
authors.forename: P
authors.initials: P
authors.lastname: Londoño
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: M E
authors.initials: ME
authors.lastname: Selkirk
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D000918:Antibody Specificity; D000947:Antigens, Helminth / Q000235:genetics; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005368:Filariasis / Q000276:immunology / Q000517:prevention & control; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000276:immunology*; D006183:H-2 Antigens; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000008:administration & dosage
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D006183:H-2 Antigens; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D005979:Glutathione Peroxidase