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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752168/full |
| _version_ | 1819025334442393600 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T05:09:02Z |
| format | Article |
| id | doaj.art-a8258799504c46ed999cf3e2da625883 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T05:09:02Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a8258799504c46ed999cf3e2da6258832022-12-21T19:15:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.752168752168Multi-Antigen Outer Membrane Vesicle Engineering to Develop Polyvalent Vaccines: The Staphylococcus aureus CaseEnrico König0Assunta Gagliardi1Ilary Riedmiller2Chiara Andretta3Michele Tomasi4Carmela Irene5Luca Frattini6Ilaria Zanella7Francesco Berti8Alberto Grandi9Alberto Grandi10Elena Caproni11Laura Fantappiè12Guido Grandi13Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyERC Vaccibiome Unit, Toscana Life Sciences Foundation, Siena, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyTechnical Research and Development, GlaxoSmithKline Vaccines, Siena, ItalyERC Vaccibiome Unit, Toscana Life Sciences Foundation, Siena, ItalyInfectious Diseases and Cancer Immunotherapy Unit, BiOMViS Srl, Siena, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyERC Vaccibiome Unit, Toscana Life Sciences Foundation, Siena, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, ItalyModification 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.752168/fullStaphylococcus aureusouter membrane vesicles (OMVs)chimeric proteinsmultivalent vaccinesOMV engineering |
| spellingShingle | 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 Frontiers in Immunology Staphylococcus aureus outer membrane vesicles (OMVs) chimeric proteins multivalent vaccines OMV engineering |
| title | 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_short | 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 |
| topic | Staphylococcus aureus outer membrane vesicles (OMVs) chimeric proteins multivalent vaccines OMV engineering |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752168/full |
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