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

tetano

Editor, Senior Moderator
J Control Release. 2017 Aug 24;264:55-65. doi: 10.1016/j.jconrel.2017.08.020. [Epub ahead of print]
[h=1]Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus.[/h] Deng L[SUP]1[/SUP], Roose K[SUP]1[/SUP], Job ER[SUP]1[/SUP], De Rycke R[SUP]2[/SUP], Van Hamme E[SUP]3[/SUP], Gon?alves A[SUP]3[/SUP], Parthoens E[SUP]3[/SUP], Cicchelero L[SUP]4[/SUP], Sanders N[SUP]4[/SUP], Fiers W[SUP]5[/SUP], Saelens X[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.
Copyright ? 2017. Published by Elsevier B.V.


[h=4]KEYWORDS:[/h] Bacteriophage; Escherichia coli; Influenza; Live oral vaccine

PMID: 28842314 DOI: 10.1016/j.jconrel.2017.08.020
 
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