title: Recombinant (F1+V) vaccine protects cynomolgus macaques against pneumonic plague.
abstract: Cynomolgus macaques, immunised at the 80 μg dose level with an rF1+rV vaccine (two doses, three weeks apart), were fully protected against pneumonic plague following inhalational exposure to a clinical isolate of Yersinia pestis (strain CO92) at week 8 of the schedule. At this time, all the immunised animals had developed specific IgG titres to rF1 and rV with geometric mean titres of 96.83±20.93 μg/ml and 78.59±12.07 μg/ml, respectively, for the 40 μg dose group; by comparison, the 80 μg dose group had developed titres of 114.4±22.1 and 90.8±15.8 μg/ml to rF1 and rV, respectively, by week 8. For all the immunised animals, sera drawn at week 8 competed with the neutralising and protective Mab7.3 for binding to rV antigen in a competitive ELISA, indicating that a functional antibody response to rV had been induced. All but one of the group immunised at the lower 40 μg dose-level were protected against infection; the single animal which succumbed had significantly reduced antibody responses to both the rF1 and rV antigens. Although a functional titre to rV antigen was detected for this animal, this was insufficient for protection, indicating that there may have been a deficiency in the functional titre to rF1 and underlining the need for immunity to both vaccine antigens to achieve protective efficacy against plague. This candidate vaccine, which has been evaluated as safe and immunogenic in clinical studies, has now been demonstrated to protect cynomolgus macaques, immunised in the clinical regimen, against pneumonic plague.
authors.affiliation: Dstl PortonDown, Salisbury, Wilts SP4 0JQ, UK. dewilliamson@dstl.gov.uk
authors.forename: E D
authors.initials: ED
authors.lastname: Williamson
authors.forename: P J
authors.initials: PJ
authors.lastname: Packer
authors.forename: E L
authors.initials: EL
authors.lastname: Waters
authors.forename: A J
authors.initials: AJ
authors.lastname: Simpson
authors.forename: D
authors.initials: D
authors.lastname: Dyer
authors.forename: J
authors.initials: J
authors.lastname: Hartings
authors.forename: N
authors.initials: N
authors.lastname: Twenhafel
authors.forename: M L M
authors.initials: ML
authors.lastname: Pitt
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007117:Immunization, Secondary / Q000379:methods; D008252:Macaca fascicularis; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018419:Primate Diseases / Q000517:prevention & control; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014614:Vaccines, Synthetic; C086725:caf1 protein, Yersinia pestis