AUTHOR=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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.583008

DOI=10.3389/fimmu.2020.583008

ISSN=1664-3224

ABSTRACT=<p>Infections caused by the opportunistic pathogen <italic>Pseudomonas aeruginosa</italic> 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 <italic>Pseudomonas</italic> infections. Here we describe a novel subunit vaccine that targets the <italic>P. aeruginosa</italic> 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 <italic>in vitro</italic> and elicits strong IgG and IgA titers in mice when administered intranasally. This self-adjuvanting vaccine expedites the clearance of <italic>P. aeruginosa</italic> 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.</p>