Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case

Modification of surface antigens and differential expression of virulence factors are frequent strategies pathogens adopt to escape the host immune system. These escape mechanisms make pathogens a “moving target” for our immune system and represent a challenge for the development of vaccines, which...

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Autores principales:	Enrico König, Assunta Gagliardi, Ilary Riedmiller, Chiara Andretta, Michele Tomasi, Carmela Irene, Luca Frattini, Ilaria Zanella, Francesco Berti, Alberto Grandi, Elena Caproni, Laura Fantappiè, Guido Grandi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Staphylococcus aureus outer membrane vesicles (OMVs) chimeric proteins multivalent vaccines OMV engineering Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/a8258799504c46ed999cf3e2da625883
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spelling	oai:doaj.org-article:a8258799504c46ed999cf3e2da6258832021-11-08T07:06:55ZMulti-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case1664-322410.3389/fimmu.2021.752168https://doaj.org/article/a8258799504c46ed999cf3e2da6258832021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.752168/fullhttps://doaj.org/toc/1664-3224Modification of surface antigens and differential expression of virulence factors are frequent strategies pathogens adopt to escape the host immune system. These escape mechanisms make pathogens a “moving target” for our immune system and represent a challenge for the development of vaccines, which require more than one antigen to be efficacious. Therefore, the availability of strategies, which simplify vaccine design, is highly desirable. Bacterial Outer Membrane Vesicles (OMVs) are a promising vaccine platform for their built-in adjuvanticity, ease of purification and flexibility to be engineered with foreign proteins. However, data on if and how OMVs can be engineered with multiple antigens is limited. In this work, we report a multi-antigen expression strategy based on the co-expression of two chimeras, each constituted by head-to-tail fusions of immunogenic proteins, in the same OMV-producing strain. We tested the strategy to develop a vaccine against Staphylococcus aureus, a Gram-positive human pathogen responsible for a large number of community and hospital-acquired diseases. Here we describe an OMV-based vaccine in which four S. aureus virulent factors, ClfAY338A, LukE, SpAKKAA and HlaH35L have been co-expressed in the same OMVs (CLSH-OMVsΔ60). The vaccine elicited antigen-specific antibodies with functional activity, as judged by their capacity to promote opsonophagocytosis and to inhibit Hla-mediated hemolysis, LukED-mediated leukocyte killing, and ClfA-mediated S. aureus binding to fibrinogen. Mice vaccinated with CLSH-OMVsΔ60 were robustly protected from S. aureus challenge in the skin, sepsis and kidney abscess models. This study not only describes a generalized approach to develop easy-to-produce and inexpensive multi-component vaccines, but also proposes a new tetravalent vaccine candidate ready to move to development.Enrico KönigAssunta GagliardiIlary RiedmillerChiara AndrettaMichele TomasiCarmela IreneLuca FrattiniIlaria ZanellaFrancesco BertiAlberto GrandiAlberto GrandiElena CaproniLaura FantappièGuido GrandiFrontiers Media S.A.articleStaphylococcus aureusouter membrane vesicles (OMVs)chimeric proteinsmultivalent vaccinesOMV engineeringImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus outer membrane vesicles (OMVs) chimeric proteins multivalent vaccines OMV engineering Immunologic diseases. Allergy RC581-607
spellingShingle	Staphylococcus aureus outer membrane vesicles (OMVs) chimeric proteins multivalent vaccines OMV engineering Immunologic diseases. Allergy RC581-607 Enrico König Assunta Gagliardi Ilary Riedmiller Chiara Andretta Michele Tomasi Carmela Irene Luca Frattini Ilaria Zanella Francesco Berti Alberto Grandi Alberto Grandi Elena Caproni Laura Fantappiè Guido Grandi Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
description	Modification of surface antigens and differential expression of virulence factors are frequent strategies pathogens adopt to escape the host immune system. These escape mechanisms make pathogens a “moving target” for our immune system and represent a challenge for the development of vaccines, which require more than one antigen to be efficacious. Therefore, the availability of strategies, which simplify vaccine design, is highly desirable. Bacterial Outer Membrane Vesicles (OMVs) are a promising vaccine platform for their built-in adjuvanticity, ease of purification and flexibility to be engineered with foreign proteins. However, data on if and how OMVs can be engineered with multiple antigens is limited. In this work, we report a multi-antigen expression strategy based on the co-expression of two chimeras, each constituted by head-to-tail fusions of immunogenic proteins, in the same OMV-producing strain. We tested the strategy to develop a vaccine against Staphylococcus aureus, a Gram-positive human pathogen responsible for a large number of community and hospital-acquired diseases. Here we describe an OMV-based vaccine in which four S. aureus virulent factors, ClfAY338A, LukE, SpAKKAA and HlaH35L have been co-expressed in the same OMVs (CLSH-OMVsΔ60). The vaccine elicited antigen-specific antibodies with functional activity, as judged by their capacity to promote opsonophagocytosis and to inhibit Hla-mediated hemolysis, LukED-mediated leukocyte killing, and ClfA-mediated S. aureus binding to fibrinogen. Mice vaccinated with CLSH-OMVsΔ60 were robustly protected from S. aureus challenge in the skin, sepsis and kidney abscess models. This study not only describes a generalized approach to develop easy-to-produce and inexpensive multi-component vaccines, but also proposes a new tetravalent vaccine candidate ready to move to development.
format	article
author	Enrico König Assunta Gagliardi Ilary Riedmiller Chiara Andretta Michele Tomasi Carmela Irene Luca Frattini Ilaria Zanella Francesco Berti Alberto Grandi Alberto Grandi Elena Caproni Laura Fantappiè Guido Grandi
author_facet	Enrico König Assunta Gagliardi Ilary Riedmiller Chiara Andretta Michele Tomasi Carmela Irene Luca Frattini Ilaria Zanella Francesco Berti Alberto Grandi Alberto Grandi Elena Caproni Laura Fantappiè Guido Grandi
author_sort	Enrico König
title	Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
title_short	Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
title_full	Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
title_fullStr	Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
title_full_unstemmed	Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case
title_sort	multi-antigen outer membrane vesicle engineering to develop polyvalent vaccines: the staphylococcus aureus case
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a8258799504c46ed999cf3e2da625883
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Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus Case

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