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Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus

Lei Deng (UGent) , Kenny Roose (UGent) , Emma Job (UGent) , Riet De Rycke (UGent) , Evelien Van Hamme (UGent) , Amanda Gonçalves (UGent) , Eef Parthoens (UGent) , Laetitia Cicchelero E (UGent) , Niek Sanders (UGent) , Walter Fiers (UGent) , et al.
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Abstract
We describe a novel live oral vaccine type. Conceptually, this vaccine is based on a non-lytic, recombinant filamentous bacteriophage that displays an antigen of interest. To provide proof of concept we used the amino-terminal part of a conserved influenza A virus epitope, i.e. matrix protein 2 ectodomain (M2e) residues 2 to 16, as the antigen of interest. Rather than using the phages as purified virus-like particles as a vaccine, these phages were delivered to intestinal Peyer's patches as a live bacterium-phage combination that comprises Escherichia coli cells that conditionally express invasin derived from Yersinia pseudotuberculosis. Invasin-expressing E. coli cells were internalized by mammalian Hep-2 cells in vitro and adhered to mouse intestinal microfold (M) cells ex vivo. Invasin-expressing E. coli cells were permissive for recombinant filamentous bacteriophage f88 that displays M2e and became persistently infected. Oral administration of the live engineered E. coli-invasin-phage combination to mice induced M2e-specific serum IgG antibodies. Mice that had been immunized with invasin-expressing E. coli cells that carried M2e2-16 displaying fd phages seroconverted to M2e and showed partial protection against challenge with influenza A virus. Oral delivery of a live vaccine comprising a bacterial host that is targeted to Peyer's patches and is persistently infected with an antigen-displaying phage, can thus be exploited as an oral vaccine.
Keywords
Live oral vaccine, Influenza, Escherichia coli, Bacteriophage, PSEUDOTUBERCULOSIS INVASIN PROTEIN, PATCH M CELLS, MATRIX PROTEIN-2, MAMMALIAN-CELLS, PEYERS-PATCHES, STEM-CELLS, VACCINE, RECEPTORS, YERSINIA, DOMAIN

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Chicago
Deng, Lei, Kenny Roose, Emma Job, Riet De Rycke, Evelien Van Hamme, Amanda Gonçalves, Eef Parthoens, et al. 2017. “Oral Delivery of Escherichia Coli Persistently Infected with M2e-displaying Bacteriophages Partially Protects Against Influenza A Virus.” Journal of Controlled Release 264: 55–65.
APA
Deng, L., Roose, K., Job, E., De Rycke, R., Van Hamme, E., Gonçalves, A., Parthoens, E., et al. (2017). Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus. JOURNAL OF CONTROLLED RELEASE, 264, 55–65.
Vancouver
1.
Deng L, Roose K, Job E, De Rycke R, Van Hamme E, Gonçalves A, et al. Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus. JOURNAL OF CONTROLLED RELEASE. 2017;264:55–65.
MLA
Deng, Lei, Kenny Roose, Emma Job, et al. “Oral Delivery of Escherichia Coli Persistently Infected with M2e-displaying Bacteriophages Partially Protects Against Influenza A Virus.” JOURNAL OF CONTROLLED RELEASE 264 (2017): 55–65. Print.
@article{8537864,
  abstract     = {We describe a novel live oral vaccine type. Conceptually, this vaccine is based on a non-lytic, recombinant filamentous bacteriophage that displays an antigen of interest. To provide proof of concept we used the amino-terminal part of a conserved influenza A virus epitope, i.e. matrix protein 2 ectodomain (M2e) residues 2 to 16, as the antigen of interest. Rather than using the phages as purified virus-like particles as a vaccine, these phages were delivered to intestinal Peyer's patches as a live bacterium-phage combination that comprises Escherichia coli cells that conditionally express invasin derived from Yersinia pseudotuberculosis. Invasin-expressing E. coli cells were internalized by mammalian Hep-2 cells in vitro and adhered to mouse intestinal microfold (M) cells ex vivo. Invasin-expressing E. coli cells were permissive for recombinant filamentous bacteriophage f88 that displays M2e and became persistently infected. Oral administration of the live engineered E. coli-invasin-phage combination to mice induced M2e-specific serum IgG antibodies. Mice that had been immunized with invasin-expressing E. coli cells that carried M2e2-16 displaying fd phages seroconverted to M2e and showed partial protection against challenge with influenza A virus. Oral delivery of a live vaccine comprising a bacterial host that is targeted to Peyer's patches and is persistently infected with an antigen-displaying phage, can thus be exploited as an oral vaccine.},
  author       = {Deng, Lei and Roose, Kenny and Job, Emma and De Rycke, Riet and Van Hamme, Evelien and Gon\c{c}alves, Amanda and Parthoens, Eef and Cicchelero E, Laetitia and Sanders, Niek and Fiers, Walter and Saelens, Xavier},
  issn         = {0168-3659},
  journal      = {JOURNAL OF CONTROLLED RELEASE},
  keyword      = {Live oral vaccine,Influenza,Escherichia coli,Bacteriophage,PSEUDOTUBERCULOSIS INVASIN PROTEIN,PATCH M CELLS,MATRIX PROTEIN-2,MAMMALIAN-CELLS,PEYERS-PATCHES,STEM-CELLS,VACCINE,RECEPTORS,YERSINIA,DOMAIN},
  language     = {eng},
  pages        = {55--65},
  title        = {Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2017.08.020},
  volume       = {264},
  year         = {2017},
}

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