title: Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.
abstract: 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.
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France.
authors: Vincent
authors: V
authors: Le Moigne
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France.
authors: Martin
authors: M
authors: Rottman
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France.
authors: Céline
authors: C
authors: Goulard
authors: IN-CELL-ART, Nantes, France.
authors: Benoît
authors: B
authors: Barteau
authors: CNRS-Aix-Marseille Université-Enzymologie Interfaciale et Physiologie de la Lipolyse UMR 7282, 31 chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors: Isabelle
authors: I
authors: Poncin
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France.
authors: Nathalie
authors: N
authors: Soismier
authors: CNRS-Aix-Marseille Université-Enzymologie Interfaciale et Physiologie de la Lipolyse UMR 7282, 31 chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors: Stéphane
authors: S
authors: Canaan
authors: INSERM UMR 1087, CNRS UMR 6291, Nantes, France; Université de Nantes, l'institut du thorax, Nantes, France.
authors: Bruno
authors: B
authors: Pitard
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France.
authors: Jean-Louis
authors: JL
authors: Gaillard
authors: INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, France. Electronic address: jean-louis.herrmann@rpc.aphp.fr.
authors: Jean-Louis
authors: JL
authors: Herrmann
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008297:Male; D051379:Mice; D009165:Mycobacterium Infections, Nontuberculous / Q000150:complications / Q000517:prevention & control*; D009170:Nontuberculous Mycobacteria / Q000201:enzymology / Q000276:immunology*; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D010738:Type C Phospholipases / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D010738:Type C Phospholipases; D001616:beta-Galactosidase
keywords: Cystic fibrosis; DNA vaccine; Mycobacteria; PLC; Pulmonary diseases; ΔF508