Functional assays to screen and select monoclonal antibodies that target Yersinia pestis .

Autor:	Biryukov SS; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Rill NO; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Klimko CP; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Dankmeyer JL; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Shoe JL; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Hunter M; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Talyansky Y; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Hau D; Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Gates-Hollingsworth MA; Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Pandit SG; Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Fetterer DP; Biostatistics Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Qiu J; Biostatistics Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., Davies ML; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA., AuCoin DP; Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Cote CK; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA.
Jazyk:	angličtina
Zdroj:	Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2023 Aug 01; Vol. 19 (2), pp. 2216085. Date of Electronic Publication: 2023 Jun 08.
DOI:	10.1080/21645515.2023.2216085
Abstrakt:	Yersinia pestis is a gram-negative bacterium that causes plague in animals and humans. Depending on the route of disease transmission, the bacterium can cause an acute, often fatal disease that has a narrow window for treatment with antibiotics. Additionally, antibiotic resistant strains have been identified, emphasizing the need for novel treatments. Antibody therapy is an appealing option that can direct the immune system to clear bacterial infections. Advances in biotechnology have made both engineering and producing antibodies easier and more affordable. In this study, two screening assays were optimized to evaluate the ability of antibodies to promote phagocytosis of Y. pestis by macrophages and to induce a cytokine signature in vitro that may be predictive of protection in vivo. We evaluated a panel of 21 mouse monoclonal antibodies targeting either the anti-phagocytic capsule F1 protein or the LcrV antigen, which is part of the type 3 secretion system that facilitates translocation of virulence factors into the host cell, using two functional assays. Anti-F1 and anti-LcrV monoclonal antibodies both increased bacterial uptake by macrophages, with greater uptake observed in the presence of antibodies that were protective in the mouse pneumonic plague model. In addition, the protective anti-F1 and anti-LcrV antibodies produced unique cytokine signatures that were also associated with in vivo protection. These antibody-dependent characteristics from in vitro functional assays will be useful in down-selecting efficacious novel antibodies that can be used for treatment of plague.
Databáze:	MEDLINE
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