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Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Oct 22; Vol. 116 (43), pp. 21780-21788. Date of Electronic Publication: 2019 Oct 07. - Publication Year :
- 2019
-
Abstract
- Bacterial outer membrane vesicles (OMVs) represent an interesting vaccine platform for their built-in adjuvanticity and simplicity of production process. Moreover, OMVs can be decorated with foreign antigens using different synthetic biology approaches. However, the optimal OMV engineering strategy, which should guarantee the OMV compartmentalization of most heterologous antigens in quantities high enough to elicit protective immune responses, remains to be validated. In this work we exploited the lipoprotein transport pathway to engineer OMVs with foreign proteins. Using 5 Staphylococcus aureus protective antigens expressed in Escherichia coli as fusions to a lipoprotein leader sequence, we demonstrated that all 5 antigens accumulated in the vesicular compartment at a concentration ranging from 5 to 20% of total OMV proteins, suggesting that antigen lipidation could be a universal approach for OMV manipulation. Engineered OMVs elicited high, saturating antigen-specific antibody titers when administered to mice in quantities as low as 0.2 μg/dose. Moreover, the expression of lipidated antigens in E. coli BL21(DE3)Δ ompA Δ msbB Δ pagP was shown to affect the lipopolysaccharide structure, with the result that the TLR4 agonist activity of OMVs was markedly reduced. These results, together with the potent protective activity of engineered OMVs observed in mice challenged with S. aureus Newman strain, makes the 5-combo-OMVs a promising vaccine candidate to be tested in clinics.<br />Competing Interests: Conflict of interest statement: G. Grandi, L. Fantappiè, and C.I. are coinventors of a patent on OMVs; A. Grandi and G. Grandi are involved in a biotech company interested in exploiting the OMV platform.<br /> (Copyright © 2019 the Author(s). Published by PNAS.)
- Subjects :
- Animals
Bacterial Outer Membrane immunology
Bacterial Outer Membrane metabolism
Bacterial Outer Membrane Proteins immunology
Bacterial Outer Membrane Proteins metabolism
Escherichia coli genetics
Escherichia coli metabolism
Female
Lipopolysaccharides immunology
Mice
Staphylococcal Infections immunology
Staphylococcal Infections microbiology
Antigens, Bacterial immunology
Bacterial Vaccines immunology
Extracellular Vesicles immunology
Staphylococcal Infections prevention & control
Staphylococcus aureus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 116
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 31591215
- Full Text :
- https://doi.org/10.1073/pnas.1905112116