4.5 Article

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

Journal

VACCINE
Volume 33, Issue 4, Pages 523-526

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.11.051

Keywords

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

Funding

  1. National Institute of Allergy and Infectious Diseases [AI052474, AI92711]
  2. American Heart Association [POST4590023]
  3. Innovation Fund of the University of Chicago Center for Technology Development Ventures

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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 SpA(KKAA)-mAb 3F6, which neutralizes the immunoglobulin Fc gamma-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 SpA(KKAA)-mAb that protects neonatal mice against S. aureus sepsis and may therefore be subjected to clinical testing in VLBW neonates. (C) 2014 Elsevier Ltd. All rights reserved.

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