| Autor: |
Karatovskaya A; Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia., Rudenko N; Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia., Zamyatina A; Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia., Zvonarev A; FSBIS FRC Pushchino Scientific Centre of Biological Research, G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, Russia., Oleinikov V; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Ulitsa Miklukho-Maklaya, Moscow, Russia., Shpirt A; Laboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia., Perepelov A; Laboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia., Knirel Y; Laboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia., Brovko F; Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia. |
| Abstrakt: |
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. |
