Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: The Mycobacterium abscessus model. Issue 18 (27th April 2015)

• Record Type: Journal Article
• Authors: Le Moigne, Vincent; Rottman, Martin; Goulard, Céline; Barteau, Benoît; Poncin, Isabelle; Soismier, Nathalie; Canaan, Stéphane; Pitard, Bruno; Gaillard, Jean-Louis; Herrmann, Jean-Louis
• Is Part Of: Vaccine. Volume 33:Issue 18(2015)
• Page Start: 2118
• Page End: 2124
• Publication Date: 2015-04-27
• Subjects: Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.03.030
• Languages: English
• ISSNs: 0264-410X

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">Vaccine strategies represent one of the fighting answers against multiresistant bacteria in a number of clinical settings like cystic fibrosis (CF). <italic>Mycobacterium abscessus</italic>, an emerging CF pathogen, raises difficult therapeutic problems due to its intrinsic antibiotic multiresistance.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">By reverse vaccinology, we identified <italic>M</italic>. <italic>abscessus</italic> phospholipase C (MA-PLC) as a potential vaccine target. We deciphered here the protective response generated by vaccination with plasmid DNA encoding the MA-PLC formulated with a tetra functional block copolymer 704, in CF (ΔF508) mice. Protection was tested against aerosolized smooth and rough (hypervirulent) variants of <italic>M. abscessus</italic>.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">MA-PLC DNA vaccination (days 0, 21, 42) elicited a strong antibody response. A significant protective effect was obtained against aerosolized <italic>M. abscessus</italic> (S variant) in ΔF508 mice, but not in wild-type FVB littermates; similar results were observed when: (i) challenging mice with the "hypervirulent" R variant, and; (ii) immunizing mice with purified MA-PLC protein. High IgG titers against MA-PLC protein were measured in CF patients with <italic>M. abscessus</italic> infection; interestingly, significant titers were also detected in CF patients positive for <italic>Pseudomonas aeruginosa versus P. aeruginosa</italic>-negative controls.</p> </sec> <sec> <title id="sect0025">Conclusions</title> <p id="spar0020">MA-PLC DNA- and PLC protein-vaccinated mice cleared more rapidly <italic>M. abscessus</italic> than β-galactosidase DNA- or PBS- vaccinated mice in the context of CF. PLCs could constitute interesting vaccine targets against common PLC-producing CF pathogens like <italic>P. aeruginosa.</italic></p> </sec> </abstract>