Characterization of a Cynomolgus Macaque Model of Pneumonic Plague Evaluating Vaccine Efficacy

1 Characterization of a Cynomolgus Macaque Model of Pneumonic Plague Evaluating 1 Vaccine Efficacy 2 3 Patricia Fellows, Jessica Price, Shannon Martin, Karen Metcalfe, Robert Krile, Roy 4 Barnewall, Mary Kate Hart and Hank Lockman 5 6 DynPort Vaccine Company LLC, A CSC Company, Frederick, MD, USA, Battelle, Columbus, 7 OH, USA 8 9 Abstract 10 Efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) 11 to establish the relationship between vaccine dosage, antibody titers and survival following 12 aerosol challenge with a lethal dosage of Yersinia pestis (Y. pestis) strain Colorado 92 (CO92). 13 CMs were vaccinated with a range of rF1V dosages using a three-dose schedule (Days 0, 56 and 14 121) to provide a range of survival outcomes. The humoral immune response following 15 vaccination was evaluated in anti-rF1, anti-rV and anti-rF1V Bridge ELISAs. Animals were 16 challenged via aerosol exposure on Day 149. Vaccine dosage levels and antibody response levels 17 were each significantly associated with probability of survival (p<0.0001) in CMs. Vaccination 18 also decreased signs of pneumonic plague in a dosage-dependent manner. There were 19 statistically significant correlations between vaccine dosage and time to onset of fever 20 (p<0.0001), time from onset of fever to death (p<0.0001), time to onset of elevated respiratory 21 rate (p=0.0003) and time to onset of decreased activity (p=0.0251) after infection in animals 22 exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were 23 associated with higher dosages of rF1V. Immunization with ≥ 12 μg rF1V resulted in 100% 24 survival in the CMs. Since both vaccine dosage and anti-rF1V antibody titers correlate with 25 survival, rF1V Bridge ELISA titers can be used as a correlate of protection. 26 27 CVI Accepted Manuscript Posted Online 29 July 2015 Clin. Vaccine Immunol. doi:10.1128/CVI.00290-15 Copyright © 2015, American Society for Microbiology. All Rights Reserved.