dc.contributor.author | Das, Sayan | |
dc.contributor.author | Howlader, Debaki R. | |
dc.contributor.author | Zheng, Qi | |
dc.contributor.author | Ratnakaram, Siva Sai Kumar | |
dc.contributor.author | Whittier, Sean K. | |
dc.contributor.author | Lu, Ti | |
dc.contributor.author | Keith, Johnathan D. | |
dc.contributor.author | Picking, William D. | |
dc.contributor.author | Birket, Susan E. | |
dc.contributor.author | Picking, Wendy L. | |
dc.date.accessioned | 2022-01-17T19:09:28Z | |
dc.date.available | 2022-01-17T19:09:28Z | |
dc.date.issued | 2020-11-17 | |
dc.identifier.citation | Das, S., Howlader, D. R., Zheng, Q., Ratnakaram, S., Whittier, S. K., Lu, T., Keith, J. D., Picking, W. D., Birket, S. E., & Picking, W. L. (2020). Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa. Frontiers in immunology, 11, 583008. https://doi.org/10.3389/fimmu.2020.583008 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32408 | |
dc.description.abstract | Infections 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.publisher | Frontiers Media | en_US |
dc.rights | 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). | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Pseudomonas aeruginosa | en_US |
dc.subject | Type III secretion system | en_US |
dc.subject | Vaccine | en_US |
dc.subject | IL-17 | en_US |
dc.subject | Opsonophagocytosis | en_US |
dc.subject | Protective efficacy | en_US |
dc.subject | PcrV | en_US |
dc.subject | PopB | en_US |
dc.title | Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Das, Sayan | |
kusw.kuauthor | Howlader, Debaki R. | |
kusw.kuauthor | Zheng, Qi | |
kusw.kuauthor | Ratnakaram, Siva Sai Kumar | |
kusw.kuauthor | Whittier, Sean K. | |
kusw.kuauthor | Lu, Ti | |
kusw.kuauthor | Picking, William D. | |
kusw.kuauthor | Picking, Wendy L. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.3389/fimmu.2020.583008 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7705240 | en_US |
dc.rights.accessrights | openAccess | en_US |