Protection induced by a Francisella tularensis subunit vaccine delivered by glucan particles
Authors
Whelan, Adam O.Flick-Smith, Helen C.
Homan, Jane
Shen, Zu T.
Carpenter, Zoe
Khoshkenar, Payam
Abraham, Ambily
Walker, Nicola J.
Levitz, Stuart M.
Ostroff, Gary R.
Oyston, Petra C. F.
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2018-10-08Keywords
VaccinesAntigen encapsulation
Francisella tularensis
Immune response
Mouse models
Antigen isotypes
Enzyme-linked immunoassays
Vaccination and immunization
Bacterial Infections and Mycoses
Immunity
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Therapeutics
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Show full item recordAbstract
Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead antigens: FTT1043 (Mip), IglC, FTT0814, FTT0438, FTT0071 (GltA), FTT0289, FTT0890 (PilA) prior to transitioning their evaluation to a Fischer 344 rat model for efficacy evaluation. F344 rats were vaccinated with the GP protein antigens co-delivered with GP-loaded with Francisella LPS. Measurement of cell mediated immune responses and computational epitope analysis allowed down-selection to three promising candidates: FTT0438, FTT1043 and FTT0814. Of these, a GP vaccine delivering Francisella LPS and the FTT0814 protein was able to induce protection in rats against an aerosol challenge of F. tularensis SchuS4, and reduced organ colonisation and clinical signs below that which immunisation with a GP-LPS alone vaccine provided. This is the first report of a protein supplementing protection induced by LPS in a Francisella vaccine. This paves the way for developing an effective, safe subunit vaccine for the prevention of inhalational tularemia, and validates the GP platform for vaccine delivery where complex immune responses are required for prevention of infections by intracellular pathogens.Source
PLoS One. 2018 Oct 8;13(10):e0200213. doi: 10.1371/journal.pone.0200213. eCollection 2018. Link to article on publisher's site
DOI
10.1371/journal.pone.0200213Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40825PubMed ID
30296254Related Resources
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Copyright: © 2018 Crown Copyright. This is an open access article distributed under the terms of the Creative Commons CC BY 4.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0200213
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Except where otherwise noted, this item's license is described as Copyright: © 2018 Crown Copyright. This is an open access article distributed under the terms of the Creative Commons CC BY 4.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.