title: Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus.
abstract: Staphylococcus aureus is a cause of sepsis and meningitis in very-low-birth-weight (VLBW) infants. Clinical trials with S. aureus specific antibodies failed to protect VLBW neonates, which may be due to the immune evasive attributes of staphylococcal protein A (SpA). Here we show that mouse monoclonal antibody SpAKKAA-mAb 3F6, which neutralizes the immunoglobulin Fcγ-binding and B cell receptor crosslinking attributes of SpA, protects neonatal mice against S. aureus sepsis and raises protective immunity against subsequent staphylococcal infection. We developed a humanized SpAKKAA-mAb that protects neonatal mice against S. aureus sepsis and may therefore be subjected to clinical testing in VLBW neonates.
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Vilasack
authors.initials: V
authors.lastname: Thammavongsa
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauch
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA. Electronic address: oschnee@bsd.uchicago.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016470:Bacteremia / Q000517:prevention & control; D004195:Disease Models, Animal; D016920:Meningitis, Bacterial / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013205:Staphylococcal Protein A / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D013205:Staphylococcal Protein A; D037521:Virulence Factors
keywords: Monoclonal antibody; Neonatal bacteremia and meningitis; Protective immunity; Recurrent infection; Staphylococcal protein A; Staphylococcus aureus