VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation

Abstract Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) and mounting antibiotic resistance requires innovative treatment strategies. S. aureus uses secreted cyclic autoinducing peptides (AIPs) and the accessory gene regulator (agr) operon to coordinate expressi...

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Autores principales:	Seth M. Daly, Jason A. Joyner, Kathleen D. Triplett, Bradley O. Elmore, Srijana Pokhrel, Kathryn M. Frietze, David S. Peabody, Bryce Chackerian, Pamela R. Hall
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a232fa239de454899538bbde3d06141
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spelling	oai:doaj.org-article:0a232fa239de454899538bbde3d061412021-12-02T11:52:28ZVLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation10.1038/s41598-017-00753-02045-2322https://doaj.org/article/0a232fa239de454899538bbde3d061412017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00753-0https://doaj.org/toc/2045-2322Abstract Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) and mounting antibiotic resistance requires innovative treatment strategies. S. aureus uses secreted cyclic autoinducing peptides (AIPs) and the accessory gene regulator (agr) operon to coordinate expression of virulence factors required for invasive infection. Of the four agr alleles (agr types I-IV and corresponding AIPs1-4), agr type I isolates are most frequently associated with invasive infection. Cyclization via a thiolactone bond is essential for AIP function; therefore, recognition of the cyclic form of AIP1 may be necessary for antibody-mediated neutralization. However, the small sizes of AIPs and labile thiolactone bond have hindered vaccine development. To overcome this, we used a virus-like particle (VLP) vaccine platform (PP7) for conformationally-restricted presentation of a modified AIP1 amino acid sequence (AIP1S). Vaccination with PP7-AIP1S elicited AIP1-specific antibodies and limited agr-activation in vivo. Importantly, in a murine SSTI challenge model with a highly virulent agr type I S. aureus isolate, PP7-AIP1S vaccination reduced pathogenesis and increased bacterial clearance compared to controls, demonstrating vaccine efficacy. Given the contribution of MRSA agr type I isolates to human disease, vaccine targeting of AIP1-regulated virulence could have a major clinical impact in the fight against antibiotic resistance.Seth M. DalyJason A. JoynerKathleen D. TriplettBradley O. ElmoreSrijana PokhrelKathryn M. FrietzeDavid S. PeabodyBryce ChackerianPamela R. HallNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seth M. Daly Jason A. Joyner Kathleen D. Triplett Bradley O. Elmore Srijana Pokhrel Kathryn M. Frietze David S. Peabody Bryce Chackerian Pamela R. Hall VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
description	Abstract Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) and mounting antibiotic resistance requires innovative treatment strategies. S. aureus uses secreted cyclic autoinducing peptides (AIPs) and the accessory gene regulator (agr) operon to coordinate expression of virulence factors required for invasive infection. Of the four agr alleles (agr types I-IV and corresponding AIPs1-4), agr type I isolates are most frequently associated with invasive infection. Cyclization via a thiolactone bond is essential for AIP function; therefore, recognition of the cyclic form of AIP1 may be necessary for antibody-mediated neutralization. However, the small sizes of AIPs and labile thiolactone bond have hindered vaccine development. To overcome this, we used a virus-like particle (VLP) vaccine platform (PP7) for conformationally-restricted presentation of a modified AIP1 amino acid sequence (AIP1S). Vaccination with PP7-AIP1S elicited AIP1-specific antibodies and limited agr-activation in vivo. Importantly, in a murine SSTI challenge model with a highly virulent agr type I S. aureus isolate, PP7-AIP1S vaccination reduced pathogenesis and increased bacterial clearance compared to controls, demonstrating vaccine efficacy. Given the contribution of MRSA agr type I isolates to human disease, vaccine targeting of AIP1-regulated virulence could have a major clinical impact in the fight against antibiotic resistance.
format	article
author	Seth M. Daly Jason A. Joyner Kathleen D. Triplett Bradley O. Elmore Srijana Pokhrel Kathryn M. Frietze David S. Peabody Bryce Chackerian Pamela R. Hall
author_facet	Seth M. Daly Jason A. Joyner Kathleen D. Triplett Bradley O. Elmore Srijana Pokhrel Kathryn M. Frietze David S. Peabody Bryce Chackerian Pamela R. Hall
author_sort	Seth M. Daly
title	VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
title_short	VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
title_full	VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
title_fullStr	VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
title_full_unstemmed	VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation
title_sort	vlp-based vaccine induces immune control of staphylococcus aureus virulence regulation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0a232fa239de454899538bbde3d06141
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VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation

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