title: Immunogenicity of the rF1+rV vaccine for plague with identification of potential immune correlates.
abstract: The rF1+rV candidate sub-unit vaccine for plague, formulated by adsorption to alhydrogel, has been demonstrated to be immunogenic in the cynomolgus macaque in a clinically relevant dose-range (5-40 microg of each sub-unit) and regimen. Following two doses of vaccine, a specific IgG titre developed in a dose-related manner with predominance of the IgG1/IgG2 isotypes. Groups of macaques receiving only a single dose of vaccine at the 40 microg dose-level had a significantly reduced peak IgG response and faster decline to baseline. Serum collected at week 5 from 19 immunised animals competed with and displaced murine Mab7.3 from binding to the V antigen in vitro. By week 53 of the schedule, although absolute IgG titres had declined, 17/19 macaque sera tested contained competing antibody, indicating the durability of a functional immune response to rF1+rV in this species. Thirteen of these week 53 sera were passively transferred into groups of naive mice, and all conferred full or partial protection against subsequent challenge of the mice with plague. Generally, those sera which were most competitive with Mab 7.3 for binding to V antigen were fully protective by passive transfer, although one week-53 serum sample was fully protective by passive transfer but not active by competitive ELISA. The early development of protective immunity in macaques was also indicated from the protection conferred on naive mice by the passive transfer of immune macaque serum collected at 2-10 weeks of the immunisation schedule. Serum samples from representative macaques within this time period also inhibited the Yersinia-mediated cytotoxicity of J774 macrophages in a qualitative in vitro assay of type three secretion.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wilts UK SP4 0JQ, UK. dewilliamson@dstl.gov.uk
authors.forename: E D
authors.initials: ED
authors.lastname: Williamson
authors.forename: H C
authors.initials: HC
authors.lastname: Flick-Smith
authors.forename: E
authors.initials: E
authors.lastname: Waters
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: I
authors.initials: I
authors.lastname: Hodgson
authors.forename: C S
authors.initials: CS
authors.lastname: Le Butt
authors.forename: J
authors.initials: J
authors.lastname: Hill
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007115:Immunization Schedule; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology* / Q000517:prevention & control; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic