Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague
Sergei S. Biryukov,
Hua Wu,
Jennifer L. Dankmeyer,
Nathaniel O. Rill,
Christopher P. Klimko,
Kristi A. Egland,
Jennifer L. Shoe,
Melissa Hunter,
David P. Fetterer,
Ju Qiu,
Michael L. Davies,
Christoph L. Bausch,
Eddie J. Sullivan,
Thomas Luke,
Christopher K. Cote
Affiliations
Sergei S. Biryukov
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Hua Wu
SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA
Jennifer L. Dankmeyer
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Nathaniel O. Rill
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Christopher P. Klimko
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Kristi A. Egland
SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA
Jennifer L. Shoe
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Melissa Hunter
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
David P. Fetterer
Biostatistics Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Ju Qiu
Biostatistics Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Michael L. Davies
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Christoph L. Bausch
SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA
Eddie J. Sullivan
SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA
Thomas Luke
SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA
Christopher K. Cote
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Plague is an ancient disease that continues to be of concern to both the public health and biodefense research communities. Pneumonic plague is caused by hematogenous spread of Yersinia pestis bacteria from a ruptured bubo to the lungs or by directly inhaling aerosolized bacteria. The fatality rate associated with pneumonic plague is significant unless effective antibiotic therapy is initiated soon after an early and accurate diagnosis is made. As with all bacterial pathogens, drug resistance is a primary concern when developing strategies to combat these Yersinia pestis infections in the future. While there has been significant progress in vaccine development, no FDA-approved vaccine strategy exists; thus, other medical countermeasures are needed. Antibody treatment has been shown to be effective in animal models of plague. We produced fully human polyclonal antibodies in transchromosomic bovines vaccinated with the recombinant F1-V plague vaccine. The resulting human antibodies opsonized Y. pestis bacteria in the presence of RAW264.7 cells and afforded significant protection to BALB/c mice after exposure to aerosolized Y. pestis. These data demonstrate the utility of this technology to produce large quantities of non-immunogenic anti-plague human antibodies to prevent or possibly treat pneumonic plague in human.
