Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa

View/ Open
Issue Date
2020-11-17Author
Das, Sayan
Howlader, Debaki R.
Zheng, Qi
Ratnakaram, Siva Sai Kumar
Whittier, Sean K.
Lu, Ti
Keith, Johnathan D.
Picking, William D.
Birket, Susan E.
Picking, Wendy L.
Publisher
Frontiers Media
Type
Article
Article Version
Scholarly/refereed, publisher version
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).
Metadata
Show full item recordAbstract
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.
Collections
Citation
Das 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.2020.583008
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.