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dc.contributor.authorDas, Sayan
dc.contributor.authorHowlader, Debaki R.
dc.contributor.authorZheng, Qi
dc.contributor.authorRatnakaram, Siva Sai Kumar
dc.contributor.authorWhittier, Sean K.
dc.contributor.authorLu, Ti
dc.contributor.authorKeith, Johnathan D.
dc.contributor.authorPicking, William D.
dc.contributor.authorBirket, Susan E.
dc.contributor.authorPicking, Wendy L.
dc.date.accessioned2022-09-15T19:07:18Z
dc.date.available2022-09-15T19:07:18Z
dc.date.issued2020-11-17
dc.identifier.citationDas S, Howlader DR, Zheng Q, Ratnakaram SSK, Whittier SK, Lu T, Keith JD, Picking WD, Birket SE and Picking WL (2020) Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa. Front. Immunol. 11:583008. doi: 10.3389/fimmu.2020.583008en_US
dc.identifier.urihttp://hdl.handle.net/1808/33486
dc.description.abstractInfections caused by the opportunistic pathogen Pseudomonas aeruginosa can be difficult to treat due to innate and acquired antibiotic resistance and this is exacerbated by the emergence of multi-drug resistant strains. Unfortunately, no licensed vaccine yet exists to prevent Pseudomonas infections. Here we describe a novel subunit vaccine that targets the P. aeruginosa type III secretion system (T3SS). This vaccine is based on the novel antigen PaF (Pa Fusion), a fusion of the T3SS needle tip protein, PcrV, and the first of two translocator proteins, PopB. Additionally, PaF is made self-adjuvanting by the N-terminal fusion of the A1 subunit of the mucosal adjuvant double-mutant heat-labile enterotoxin (dmLT). Here we show that this triple fusion, designated L-PaF, can activate dendritic cells in vitro and elicits strong IgG and IgA titers in mice when administered intranasally. This self-adjuvanting vaccine expedites the clearance of P. aeruginosa from the lungs of challenged mice while stimulating host expression of IL-17A, which may be important for generating a protective immune response in humans. L-PaF’s protective capacity was recapitulated in a rat pneumonia model, further supporting the efficacy of this novel fusion vaccine.en_US
dc.publisherFrontiers Mediaen_US
dc.rightsCopyright © 2020 Das, Howlader, Zheng, Ratnakaram, Whittier, Lu, Keith, Picking, Birket and Picking. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectPseudomonas aeruginosaen_US
dc.subjectType III secretion systemen_US
dc.subjectVaccineen_US
dc.subjectIL-17en_US
dc.subjectOpsonophagocytosisen_US
dc.subjectProtective efficacyen_US
dc.subjectPcrVen_US
dc.subjectPopBen_US
dc.titleDevelopment of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosaen_US
dc.typeArticleen_US
kusw.kuauthorDas, Sayan
kusw.kuauthorHowlader, Debaki R.
kusw.kuauthorZheng, Qi
kusw.kuauthorRatnakaram, Siva Sai Kumar
kusw.kuauthorWhittier, Sean K.
kusw.kuauthorLu, Ti
kusw.kuauthorPicking, William D.
kusw.kuauthorPicking, Wendy L.
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.3389/fimmu.2020.583008en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccessen_US


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Copyright © 2020 Das, Howlader, Zheng, Ratnakaram, Whittier, Lu, Keith, Picking, Birket and Picking. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Except where otherwise noted, this item's license is described as: Copyright © 2020 Das, Howlader, Zheng, Ratnakaram, Whittier, Lu, Keith, Picking, Birket and Picking. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).