Development of Anti-<i>Yersinia pestis</i> Human Antibodies with Features Required for Diagnostic and Therapeutic Applications.

Lillo, Antonietta M; Velappan, Nileena; Kelliher, Julia M; Watts, Austin J; Merriman, Samuel P; Vuyisich, Grace; Lilley, Laura M; Coombs, Kent E; Mastren, Tara; Teshima, Munehiro; Stein, Benjamin W; Wagner, Gregory L; Iyer, Srinivas; Bradbury, Andrew R M; Harris, Jennifer Foster; Dichosa, Armand E; Kozimor, Stosh A

Development of Anti-Yersinia pestis Human Antibodies with Features Required for Diagnostic and Therapeutic Applications.

Lillo, Antonietta M; Velappan, Nileena; Kelliher, Julia M; Watts, Austin J; Merriman, Samuel P; Vuyisich, Grace; Lilley, Laura M; Coombs, Kent E; Mastren, Tara; Teshima, Munehiro; Stein, Benjamin W; Wagner, Gregory L; Iyer, Srinivas; Bradbury, Andrew R M; Harris, Jennifer Foster; Dichosa, Armand E; Kozimor, Stosh A.

Afiliação

Lillo AM; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Velappan N; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Kelliher JM; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Watts AJ; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Merriman SP; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Vuyisich G; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Lilley LM; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Coombs KE; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Mastren T; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Teshima M; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Stein BW; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Wagner GL; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Iyer S; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Bradbury ARM; Specifica Inc., Santa Fe, NM, USA.
Harris JF; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Dichosa AE; Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Kozimor SA; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.

Immunotargets Ther ; 9: 299-316, 2020.

Article em En | MEDLINE | ID: mdl-33294421

ABSTRACT

ABSTRACT

BACKGROUND:

Yersinia pestis is a category A infective agent that causes bubonic, septicemic, and pneumonic plague. Notably, the acquisition of antimicrobial or multidrug resistance through natural or purposed means qualifies Y. pestis as a potential biothreat agent. Therefore, high-quality antibodies designed for accurate and sensitive Y. pestis diagnostics, and therapeutics potentiating or replacing traditional antibiotics are of utmost need for national security and public health preparedness.

METHODS:

Here, we describe a set of human monoclonal immunoglobulins (IgG1s) targeting Y. pestis fraction 1 (F1) antigen, previously derived from in vitro evolution of a phage-display library of single-chain antibodies (scFv). We extensively characterized these antibodies and their effect on bacterial and mammalian cells via ELISA, flow cytometry, mass spectrometry, spectroscopy, and various metabolic assays.

RESULTS:

Two of our anti-F1 IgG (αF1Ig 2 and αF1Ig 8) stood out for high production yield, specificity, and stability. These two antibodies were additionally attractive in that they displayed picomolar affinity, did not compete when binding Y. pestis, and retained immunoreactivity upon chemical derivatization. Most importantly, these antibodies detected <1,000 Y. pestis cells in sandwich ELISA, did not harm respiratory epithelial cells, induced Y. pestis agglutination at low concentration (350 nM), and caused apparent reduction in cell growth when radiolabeled at a nonagglutinating concentration (34 nM).