Your browser doesn't support javascript.
loading
Monoclonal Antibody Protects Against Acinetobacter baumannii Infection by Enhancing Bacterial Clearance and Evading Sepsis.
Nielsen, Travis B; Pantapalangkoor, Paul; Luna, Brian M; Bruhn, Kevin W; Yan, Jun; Dekitani, Ken; Hsieh, Sarah; Yeshoua, Brandon; Pascual, Bryan; Vinogradov, Evgeny; Hujer, Kristine M; Domitrovic, T Nicholas; Bonomo, Robert A; Russo, Thomas A; Lesczcyniecka, Magda; Schneider, Thomas; Spellberg, Brad.
Afiliação
  • Nielsen TB; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Pantapalangkoor P; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Luna BM; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Bruhn KW; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Yan J; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Dekitani K; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Hsieh S; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Yeshoua B; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Pascual B; Department of Medicine and Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles.
  • Vinogradov E; National Research Council Canada, Ottowa, Ontario.
  • Hujer KM; Louis Stokes Cleveland Veterans Affairs Medical Center.
  • Domitrovic TN; Department of Medicine.
  • Bonomo RA; Louis Stokes Cleveland Veterans Affairs Medical Center.
  • Russo TA; Department of Medicine.
  • Lesczcyniecka M; Louis Stokes Cleveland Veterans Affairs Medical Center.
  • Schneider T; Department of Medicine.
  • Spellberg B; Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio.
J Infect Dis ; 216(4): 489-501, 2017 08 15.
Article em En | MEDLINE | ID: mdl-28931235
Background: Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions. Methods: We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate. Results: C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0.5 µg/mouse (0.0167 mg/kg) markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia models of XDR A. baumannii infection. C8 was also synergistic with colistin, substantially improving survival compared to monotherapy. Treatment with C8 significantly reduced blood bacterial density, cytokine production (tumor necrosis factor α, interleukin [IL] 6, IL-1ß, and IL-10), and sepsis biomarkers. Serial in vitro passaging of A. baumannii in the presence of C8 did not cause loss of mAb binding to the bacteria, but did result in emergence of less-virulent mutants that were more susceptible to macrophage uptake. Finally, we developed a highly humanized variant of C8 that retains opsonophagocytic activity in murine and human macrophages and rescued mice from lethal infection. Conclusions: We describe a promising and novel mAb as therapy for lethal, XDR A. baumannii infections, and demonstrate that it synergistically improves outcomes in combination with antibiotics.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Acinetobacter / Sepse / Acinetobacter baumannii / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Acinetobacter / Sepse / Acinetobacter baumannii / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article