Bioengineering a bacterial pathogen to assemble its own particulate vaccine capable of inducing cellular immunity

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Author(s)
Lee, Jason W
Parlane, Natalie A
Wedlock, D Neil
Rehm, Bernd HA
Griffith University Author(s)
Year published
2017
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Many bacterial pathogens naturally form cellular inclusions. Here the immunogenicity of polyhydroxyalkanoate (PHA) inclusions and their use as particulate vaccines delivering a range of host derived antigens was assessed. Our study showed that PHA inclusions of pathogenic Pseudomonas aeruginosa are immunogenic mediating a specific cell-mediated immune response. Protein engineering of the PHA inclusion forming enzyme by translational fusion of epitopes from vaccine candidates outer membrane proteins OprI, OprF, and AlgE mediated self-assembly of PHA inclusions coated by these selected antigens. Mice vaccinated with isolated ...
View more >Many bacterial pathogens naturally form cellular inclusions. Here the immunogenicity of polyhydroxyalkanoate (PHA) inclusions and their use as particulate vaccines delivering a range of host derived antigens was assessed. Our study showed that PHA inclusions of pathogenic Pseudomonas aeruginosa are immunogenic mediating a specific cell-mediated immune response. Protein engineering of the PHA inclusion forming enzyme by translational fusion of epitopes from vaccine candidates outer membrane proteins OprI, OprF, and AlgE mediated self-assembly of PHA inclusions coated by these selected antigens. Mice vaccinated with isolated PHA inclusions produced a Th1 type immune response characterized by antigen-specific production of IFN-γ and IgG2c isotype antibodies. This cell-mediated immune response was found to be associated with the production of functional antibodies reacting with cells of various P. aeruginosa strains as well as facilitating opsonophagocytic killing. This study showed that cellular inclusions of pathogenic bacteria are immunogenic and can be engineered to display selected antigens suitable to serve as particulate subunit vaccines against infectious diseases.
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View more >Many bacterial pathogens naturally form cellular inclusions. Here the immunogenicity of polyhydroxyalkanoate (PHA) inclusions and their use as particulate vaccines delivering a range of host derived antigens was assessed. Our study showed that PHA inclusions of pathogenic Pseudomonas aeruginosa are immunogenic mediating a specific cell-mediated immune response. Protein engineering of the PHA inclusion forming enzyme by translational fusion of epitopes from vaccine candidates outer membrane proteins OprI, OprF, and AlgE mediated self-assembly of PHA inclusions coated by these selected antigens. Mice vaccinated with isolated PHA inclusions produced a Th1 type immune response characterized by antigen-specific production of IFN-γ and IgG2c isotype antibodies. This cell-mediated immune response was found to be associated with the production of functional antibodies reacting with cells of various P. aeruginosa strains as well as facilitating opsonophagocytic killing. This study showed that cellular inclusions of pathogenic bacteria are immunogenic and can be engineered to display selected antigens suitable to serve as particulate subunit vaccines against infectious diseases.
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Journal Title
Scientific Reports
Volume
7
Copyright Statement
© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Subject
Biochemistry and cell biology not elsewhere classified