1. Protective activity of anti-lipoteichoic acid monoclonal antibody in single or combination therapies in methicillin-resistant Staphylococcus aureus-induced murine sepsis models.
- Author
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Ohsawa H, Baba T, Enami J, and Hiramatsu K
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Antibodies, Bacterial, Antibodies, Monoclonal therapeutic use, Daptomycin pharmacology, Daptomycin therapeutic use, Disease Models, Animal, Drug Therapy, Combination, Humans, Linezolid pharmacology, Linezolid therapeutic use, Lipopolysaccharides metabolism, Mice, Staphylococcus aureus drug effects, Teichoic Acids metabolism, Vancomycin pharmacology, Vancomycin therapeutic use, Antibodies, Monoclonal pharmacology, Lipopolysaccharides antagonists & inhibitors, Methicillin-Resistant Staphylococcus aureus drug effects, Sepsis drug therapy, Staphylococcal Infections drug therapy, Teichoic Acids antagonists & inhibitors
- Abstract
Previously, we generated and screened a panel of monoclonal antibodies (mAbs) against methicillin-resistant Staphylococcus aureus (MRSA) to identify protective mAbs in mouse infection models. One of these mAbs, ZBIA3H, bound to lipoteichoic acid (LTA) and exerted protective effects in a mouse sepsis model. To reinforce the ability of the mAb to protect against infection, combination therapies with the mAb and antibiotics need to be examined. Therefore, herein, we studied the efficacy of ZBIA3H (in combination or alone) in a mouse sepsis model. ZBIA3H improved the survival rate in the mouse models of sepsis induced by highly virulent or refractory S. aureus (community-acquired MRSA strain MW2, vancomycin-intermediate S. aureus strain Mu3, or vancomycin-resistant S. aureus strain VRS1). Furthermore, ZBIA3H remarkably improved the survival rate in combination with antimicrobial agents (vancomycin, daptomycin, or linezolid) in mouse sepsis models. From these results we conclude that anti-LTA mAb ZBIA3H or its humanized form is a promising mAb individually, or in combination with antibiotics, against clinical refractory infection of S. aureus., Competing Interests: Declaration of Competing Interest HO and JE are employees of Zenyaku Kogyo. TB and KH have no conflicts of interest to declare., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
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