Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.
BACKGROUND
Vaccine strategies represent one of the fighting answers against multiresistant bacteria in a number of clinical settings like cystic fibrosis (CF). Mycobacterium abscessus, an emerging CF pathogen, raises difficult therapeutic problems due to its intrinsic antibiotic multiresistance.


METHODS
By reverse vaccinology, we identified M. abscessus 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 M. abscessus.


RESULTS
MA-PLC DNA vaccination (days 0, 21, 42) elicited a strong antibody response. A significant protective effect was obtained against aerosolized M. abscessus (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 M. abscessus infection; interestingly, significant titers were also detected in CF patients positive for Pseudomonas aeruginosa versus P. aeruginosa-negative controls.


CONCLUSIONS
MA-PLC DNA- and PLC protein-vaccinated mice cleared more rapidly M. abscessus 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 P. aeruginosa.
['Le Moigne|Vincent|V|', 'Rottman|Martin|M|', 'Goulard|Céline|C|', 'Barteau|Benoît|B|', 'Poncin|Isabelle|I|', 'Soismier|Nathalie|N|', 'Canaan|Stéphane|S|', 'Pitard|Bruno|B|', 'Gaillard|Jean-Louis|JL|', 'Herrmann|Jean-Louis|JL|']
D000818:Animals D000907:Antibodies, Bacterial D001428:Bacterial Vaccines D003550:Cystic Fibrosis D005260:Female D006801:Humans D007074:Immunoglobulin G D008297:Male D051379:Mice D009165:Mycobacterium Infections, Nontuberculous D009170:Nontuberculous Mycobacteria D011552:Pseudomonas Infections D011550:Pseudomonas aeruginosa D010738:Type C Phospholipases D019444:Vaccines, DNA D001616:beta-Galactosidase
Cystic fibrosis ΔF508 DNA vaccine PLC Mycobacteria Pulmonary diseases