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Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide

Acinetobacter baumannii is an antibiotic-resistant opportunistic pathogen, one of the main causes of hospital infections. There is an urgent need for the development of therapy strategies which are not based on antibiotics. Hybridoma technology was used to obtain monoclonal antibodies. The antibodie...

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Autores principales: Karatovskaya, Anna, Rudenko, Natalia, Zamyatina, Anna, Zvonarev, Anton, Oleinikov, Vladimir, Shpirt, Anna, Perepelov, Andrei, Knirel, Yuriy, Brovko, Fedor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927325/
https://www.ncbi.nlm.nih.gov/pubmed/36622150
http://dx.doi.org/10.1128/spectrum.04141-22
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author Karatovskaya, Anna
Rudenko, Natalia
Zamyatina, Anna
Zvonarev, Anton
Oleinikov, Vladimir
Shpirt, Anna
Perepelov, Andrei
Knirel, Yuriy
Brovko, Fedor
author_facet Karatovskaya, Anna
Rudenko, Natalia
Zamyatina, Anna
Zvonarev, Anton
Oleinikov, Vladimir
Shpirt, Anna
Perepelov, Andrei
Knirel, Yuriy
Brovko, Fedor
author_sort Karatovskaya, Anna
collection PubMed
description Acinetobacter baumannii is an antibiotic-resistant opportunistic pathogen, one of the main causes of hospital infections. There is an urgent need for the development of therapy strategies which are not based on antibiotics. Hybridoma technology was used to obtain monoclonal antibodies. The antibodies were characterized by enzyme immunoassay and fluorescence microscopy according to their ability to opsonize A. baumannii and to protect model animals from infection upon intraperitoneal and pulmonary injection. Monoclonal antibodies (MAbs), IgG, against the K9 capsular polysaccharide (CPS) of A. baumannii were prepared using a glycoconjugate, synthesized by squaric-acid chemistry, consisting of two CPS K9 monomer units and a carrier protein. The MAbs were highly specific, stained the bacterial surface, allowed detection of A. baumannii in infected lung tissue, effectively opsonized the bacteria at nanogram concentrations (up to 1.5 ng/mL for CPS-407), and demonstrated a high ability to protect an organism against bacterial infection upon intraperitoneal and lung injection. In intraperitoneal infection of a mouse model with A. baumannii K9, the CPS-407 antibody protected at a dose of 25 μg/mouse. When bacteria were injected into the lung, MAb therapy prevented infection of the body and led to a significant reduction of the bacterial load in infected tissues. IMPORTANCE MAbs detected A. baumannii in infected lung tissue, effectively opsonized bacteria, and protected model animals from infection.
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spelling pubmed-99273252023-02-15 Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide Karatovskaya, Anna Rudenko, Natalia Zamyatina, Anna Zvonarev, Anton Oleinikov, Vladimir Shpirt, Anna Perepelov, Andrei Knirel, Yuriy Brovko, Fedor Microbiol Spectr Research Article Acinetobacter baumannii is an antibiotic-resistant opportunistic pathogen, one of the main causes of hospital infections. There is an urgent need for the development of therapy strategies which are not based on antibiotics. Hybridoma technology was used to obtain monoclonal antibodies. The antibodies were characterized by enzyme immunoassay and fluorescence microscopy according to their ability to opsonize A. baumannii and to protect model animals from infection upon intraperitoneal and pulmonary injection. Monoclonal antibodies (MAbs), IgG, against the K9 capsular polysaccharide (CPS) of A. baumannii were prepared using a glycoconjugate, synthesized by squaric-acid chemistry, consisting of two CPS K9 monomer units and a carrier protein. The MAbs were highly specific, stained the bacterial surface, allowed detection of A. baumannii in infected lung tissue, effectively opsonized the bacteria at nanogram concentrations (up to 1.5 ng/mL for CPS-407), and demonstrated a high ability to protect an organism against bacterial infection upon intraperitoneal and lung injection. In intraperitoneal infection of a mouse model with A. baumannii K9, the CPS-407 antibody protected at a dose of 25 μg/mouse. When bacteria were injected into the lung, MAb therapy prevented infection of the body and led to a significant reduction of the bacterial load in infected tissues. IMPORTANCE MAbs detected A. baumannii in infected lung tissue, effectively opsonized bacteria, and protected model animals from infection. American Society for Microbiology 2023-01-09 /pmc/articles/PMC9927325/ /pubmed/36622150 http://dx.doi.org/10.1128/spectrum.04141-22 Text en Copyright © 2023 Karatovskaya et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Karatovskaya, Anna
Rudenko, Natalia
Zamyatina, Anna
Zvonarev, Anton
Oleinikov, Vladimir
Shpirt, Anna
Perepelov, Andrei
Knirel, Yuriy
Brovko, Fedor
Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title_full Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title_fullStr Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title_full_unstemmed Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title_short Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide
title_sort protective capacity of monoclonal antibodies against acinetobacter baumannii k9 capsular polysaccharide
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927325/
https://www.ncbi.nlm.nih.gov/pubmed/36622150
http://dx.doi.org/10.1128/spectrum.04141-22
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