Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.
Vaccine
; 33(18): 2118-24, 2015 Apr 27.
Article
em En
| MEDLINE
| ID: mdl-25804706
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 ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases Tipo C
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Vacinas Bacterianas
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Vacinas de DNA
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Fibrose Cística
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Micobactérias não Tuberculosas
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Infecções por Mycobacterium não Tuberculosas
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Vaccine
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
França