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Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa
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.
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.
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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.
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Date
2020-11-17
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Frontiers Media
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Keywords
Pseudomonas aeruginosa, Type III secretion system, Vaccine, IL-17, Opsonophagocytosis, Protective efficacy, PcrV, PopB
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