Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach.
Int J Nanomedicine
; 13: 3689-3711, 2018.
Article
en En
| MEDLINE
| ID: mdl-29983563
ABSTRACT
BACKGROUND:
Adjuvants have the potential to increase the efficacy of protein-based vaccines but need to be maintained within specific temperature and storage conditions. Lyophilization can be used to increase the thermostability of protein pharmaceuticals; however, no marketed vaccine that contains an adjuvant is currently lyophilized, and lyophilization of oil-in-water nanoemulsion adjuvants presents a specific challenge. We have previously demonstrated the feasibility of lyophilizing a candidate adjuvanted protein vaccine against Mycobacterium tuberculosis (Mtb), ID93 + GLA-SE, and the subsequent improvement of thermostability; however, further development is required to prevent physicochemical changes and degradation of the TLR4 agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water nanoemulsion (SE). MATERIALS ANDMETHODS:
In this study, we took a systematic approach to the development of a thermostable product by first identifying compatible solution conditions and stabilizing excipients for both antigen and adjuvant. Next, we applied a design-of-experiments approach to identify stable lyophilized drug product formulations.RESULTS:
We identified specific formulations that contain disaccharide or a combination of disaccharide and mannitol that can achieve substantially improved thermostability and maintain immunogenicity in a mouse model when tested in accelerated and real-time stability studies.CONCLUSION:
These efforts will aid in the development of a platform formulation for use with other similar vaccines.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Temperatura
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Adyuvantes Inmunológicos
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Vacunas contra la Tuberculosis
/
Emulsiones
/
Nanopartículas
Límite:
Animals
Idioma:
En
Revista:
Int J Nanomedicine
Año:
2018
Tipo del documento:
Article
Pais de publicación:
NEW ZEALAND
/
NOVA ZELÂNDIA
/
NUEVA ZELANDA
/
NZ