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Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice

The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon inv...

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Autores principales: Kim, Hwan Keun, Cheng, Alice G., Kim, Hye-Young, Missiakas, Dominique M., Schneewind, Olaf
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931167/
https://www.ncbi.nlm.nih.gov/pubmed/20713595
http://dx.doi.org/10.1084/jem.20092514
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author Kim, Hwan Keun
Cheng, Alice G.
Kim, Hye-Young
Missiakas, Dominique M.
Schneewind, Olaf
author_facet Kim, Hwan Keun
Cheng, Alice G.
Kim, Hye-Young
Missiakas, Dominique M.
Schneewind, Olaf
author_sort Kim, Hwan Keun
collection PubMed
description The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S. aureus surface molecule that binds to Fcγ of immunoglobulin (Ig) and to the Fab portion of V(H)3-type B cell receptors, thereby interfering with opsonophagocytic clearance of the pathogen and ablating adaptive immune responses. We show that mutation of each of the five Ig-binding domains of SpA with amino acid substitutions abolished the ability of the resulting variant SpA(KKAA) to bind Fcγ or Fab V(H)3 and promote B cell apoptosis. Immunization of mice with SpA(KKAA) raised antibodies that blocked the virulence of staphylococci, promoted opsonophagocytic clearance, and protected mice against challenge with highly virulent MRSA strains. Furthermore, SpA(KKAA) immunization enabled MRSA-challenged mice to mount antibody responses to many different staphylococcal antigens.
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spelling pubmed-29311672011-02-28 Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice Kim, Hwan Keun Cheng, Alice G. Kim, Hye-Young Missiakas, Dominique M. Schneewind, Olaf J Exp Med Brief Definitive Report The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S. aureus surface molecule that binds to Fcγ of immunoglobulin (Ig) and to the Fab portion of V(H)3-type B cell receptors, thereby interfering with opsonophagocytic clearance of the pathogen and ablating adaptive immune responses. We show that mutation of each of the five Ig-binding domains of SpA with amino acid substitutions abolished the ability of the resulting variant SpA(KKAA) to bind Fcγ or Fab V(H)3 and promote B cell apoptosis. Immunization of mice with SpA(KKAA) raised antibodies that blocked the virulence of staphylococci, promoted opsonophagocytic clearance, and protected mice against challenge with highly virulent MRSA strains. Furthermore, SpA(KKAA) immunization enabled MRSA-challenged mice to mount antibody responses to many different staphylococcal antigens. The Rockefeller University Press 2010-08-30 /pmc/articles/PMC2931167/ /pubmed/20713595 http://dx.doi.org/10.1084/jem.20092514 Text en © 2010 Kim et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Kim, Hwan Keun
Cheng, Alice G.
Kim, Hye-Young
Missiakas, Dominique M.
Schneewind, Olaf
Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title_full Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title_fullStr Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title_full_unstemmed Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title_short Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
title_sort nontoxigenic protein a vaccine for methicillin-resistant staphylococcus aureus infections in mice
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931167/
https://www.ncbi.nlm.nih.gov/pubmed/20713595
http://dx.doi.org/10.1084/jem.20092514
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