Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model.
Eur J Pharm Biopharm
; 87(2): 310-7, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24434202
ABSTRACT
Next generation vaccine adjuvants include Toll like receptor agonists, which are mostly extracted from microorganisms, but synthetic small molecule TLR agonists have also been identified. However, their delivery systems have not been optimized for effective administration in conjunction with antigens. Here, we describe a novel approach in which a small molecule TLR agonist was directly conjugated to antigen to ensure effective co-delivery. We describe the conjugation of a recombinant protective antigen from Streptococcus pneumoniae linked to a TLR7 agonist. Following thorough characterization to ensure no aggregation, the conjugate was evaluated in a murine infection model. Results showed that the conjugate extended the animals' survival after lethal challenge with S. pneumoniae. Comparable results were obtained with a dose 10-fold lower than that of the native unconjugated antigen. Notably, the animals immunized with the same dose of unconjugated TLR7 agonist and antigen showed no adjuvant effect. The increased immunogenicity was likely a consequence of the co-localization of TLR7 agonist and antigen by chemical binding and was more effective than simple co-administration. This approach can be adopted to increase potency of a broad variety of antigens and reduce the dose of antigen required to induce protective immunity.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Pneumocócicas
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Streptococcus pneumoniae
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Glicoproteínas de Membrana
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Adjuvantes Imunológicos
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Imunoconjugados
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Vacinas Pneumocócicas
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Receptor 7 Toll-Like
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Antígenos de Bactérias
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article