Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus

Vaccine. 2015 Jan 15;33(4):523-6. doi: 10.1016/j.vaccine.2014.11.051. Epub 2014 Dec 6.

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.

Keywords: Monoclonal antibody; Neonatal bacteremia and meningitis; Protective immunity; Recurrent infection; Staphylococcal protein A; Staphylococcus aureus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Bacterial / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Bacteremia / prevention & control
  • Disease Models, Animal
  • Meningitis, Bacterial / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Protein A / immunology*
  • Staphylococcus aureus / immunology*
  • Survival Analysis
  • Treatment Outcome
  • Virulence Factors / immunology*

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Staphylococcal Protein A
  • Virulence Factors