Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria.
Nano Lett
; 19(7): 4760-4769, 2019 07 10.
Article
em En
| MEDLINE
| ID: mdl-31184899
ABSTRACT
Infections caused by multidrug-resistant Gram-negative bacteria have emerged as a major threat to public health worldwide. The high mortality and prevalence, along with the slow pace of new antibiotic discovery, highlight the necessity for new disease management paradigms. Here, we report on the development of a multiantigenic nanotoxoid vaccine based on macrophage membrane-coated nanoparticles for eliciting potent immunity against pathogenic Pseudomonas aeruginosa. The design of this biomimetic nanovaccine leverages the specific role of macrophages in clearing pathogens and their natural affinity for various virulence factors secreted by the bacteria. It is demonstrated that the macrophage nanotoxoid is able to display a wide range of P. aeruginosa antigens, and the safety of the formulation is confirmed both in vitro and in vivo. When used to vaccinate mice via different administration routes, the nanotoxoid is capable of eliciting strong humoral immune responses that translate into enhanced protection against live bacterial infection in a pneumonia model. Overall, the work presented here provides new insights into the design of safe, multiantigenic antivirulence vaccines using biomimetic nanotechnology and the application of these nanovaccines toward the prevention of difficult-to-treat Gram-negative infections.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Toxoides
/
Vacinas Bacterianas
/
Vacinação
/
Farmacorresistência Bacteriana
/
Fatores de Virulência
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos