title: Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.
abstract: The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P < 0.0001). Vaccination also decreased signs of pneumonic plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection.
authors.affiliation: DynPort Vaccine Company LLC, a CSC Company, Frederick, Maryland, USA pfellows@csc.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fellows
authors.affiliation: DynPort Vaccine Company LLC, a CSC Company, Frederick, Maryland, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Price
authors.affiliation: DynPort Vaccine Company LLC, a CSC Company, Frederick, Maryland, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Martin
authors.affiliation: DynPort Vaccine Company LLC, a CSC Company, Frederick, Maryland, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Metcalfe
authors.affiliation: Battelle, Columbus, Ohio, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Krile
authors.affiliation: Battelle, Columbus, Ohio, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Barnewall
authors.affiliation: DynPort Vaccine Company LLC, a CSC Company, Frederick, Maryland, USA.
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Hart
authors.affiliation: Battelle, Columbus, Ohio, USA.
authors.forename: Hank
authors.initials: H
authors.lastname: Lockman
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056724:Immunity, Humoral; D007115:Immunization Schedule; D008252:Macaca fascicularis; D010930:Plague / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D010931:Plague Vaccine; D014614:Vaccines, Synthetic