title: Protection against plague following immunisation with microencapsulated V antigen is reduced by co-encapsulation with IFN-gamma or IL-4, but not IL-6.
abstract: We have investigated intranasal delivery of novel vaccines for plague, based on poly-L-lactide (PLLA) microencapsulated recombinant V antigen (rV) of Yersinia pestis. Microspheres containing rV alone or co-encapsulated with the cytokines IFN-gamma, IL-4 or IL-6 were administered in a two-dose regimen and antibody responses and protective efficacy were monitored. All treatment groups stimulated high rV-specific antibody titres in serum, predominantly of the IgG1 isotype, which were maintained over several months. There was evidence of both IgG and IgA responses in lung samples from all groups. Formulations based on rV antigen alone or rV co-encapsulated with IL-6 provided complete protection against systemic challenge with Y. pestis strain GB; however protective efficacy was impaired by co-encapsulating either IFN-gamma or IL-4 with rV.
authors.affiliation: Dstl Biomedical Sciences, Porton Down, Salisbury, SP4 0JQ, Wiltshire, UK. kgriffin@dstl.gov.uk
authors.forename: K F
authors.initials: KF
authors.lastname: Griffin
authors.forename: J E
authors.initials: JE
authors.lastname: Eyles
authors.forename: I D
authors.initials: ID
authors.lastname: Spiers
authors.forename: H O
authors.initials: HO
authors.lastname: Alpar
authors.forename: E D
authors.initials: ED
authors.lastname: Williamson
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D004339:Drug Compounding; D005260:Female; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000627:therapeutic use*; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D052899:Pore Forming Cytotoxic Proteins; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015850:Interleukin-6; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma