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

Vilasack Thammavongsa; Sabine Rauch; Hwan Keun Kim; Dominique M. Missiakas; Olaf Schneewind

doi:10.1016/j.vaccine.2014.11.051

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

Vilasack Thammavongsa
, Sabine Rauch
, Hwan Keun Kim
, Dominique M. Missiakas
, Olaf Schneewind

Microbiology and Immunology

The University of Chicago

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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 SpA_KKAA-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 SpA_KKAA-mAb that protects neonatal mice against S. aureus sepsis and may therefore be subjected to clinical testing in VLBW neonates.

Original language	English
Pages (from-to)	523-526
Number of pages	4
Journal	Vaccine
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.vaccine.2014.11.051
State	Published - Jan 15 2015

Keywords

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

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10.1016/j.vaccine.2014.11.051

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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.",

keywords = "Monoclonal antibody, Neonatal bacteremia and meningitis, Protective immunity, Recurrent infection, Staphylococcal protein A, Staphylococcus aureus",

author = "Vilasack Thammavongsa and Sabine Rauch and Kim, \{Hwan Keun\} and Missiakas, \{Dominique M.\} and Olaf Schneewind",

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T1 - Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus

AU - Thammavongsa, Vilasack

AU - Rauch, Sabine

AU - Kim, Hwan Keun

AU - Missiakas, Dominique M.

AU - Schneewind, Olaf

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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.

AB - 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.

KW - Monoclonal antibody

KW - Neonatal bacteremia and meningitis

KW - Protective immunity

KW - Recurrent infection

KW - Staphylococcal protein A

KW - Staphylococcus aureus

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DO - 10.1016/j.vaccine.2014.11.051

M3 - Article

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SN - 0264-410X

VL - 33

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JO - Vaccine

JF - Vaccine

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ER -

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

Abstract

Keywords

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