Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach

Ryan M Kramer, Michelle C Archer, Mark T Orr, Natasha Dubois Cauwelaert, Elyse A Beebe, Po-wei D Huang, Quinton M Dowling, Alicia M Schwartz, Dawn M Fedor, Thomas S Vedvick, Christopher B Fox Infectious Disease Research Institute, Seattle, WA, USA Background: Adjuvants have the potential to increa...

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Autores principales:	Kramer RM, Archer MC, Orr MT, Dubois Cauwelaert N, Beebe EA, Huang PWD, Dowling QM, Schwartz AM, Fedor DM, Vedvick TS, Fox CB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Adjuvant Lyophilization Tuberculosis Formulation Development Design of experiments Controlled temperature chain Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/77071a8c5e9b459690ee594b3567806d
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spelling	oai:doaj.org-article:77071a8c5e9b459690ee594b3567806d2021-12-02T04:21:42ZDevelopment of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach1178-2013https://doaj.org/article/77071a8c5e9b459690ee594b3567806d2018-06-01T00:00:00Zhttps://www.dovepress.com/development-of-a-thermostable-nanoemulsion-adjuvanted-vaccine-against--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ryan M Kramer, Michelle C Archer, Mark T Orr, Natasha Dubois Cauwelaert, Elyse A Beebe, Po-wei D Huang, Quinton M Dowling, Alicia M Schwartz, Dawn M Fedor, Thomas S Vedvick, Christopher B Fox Infectious Disease Research Institute, Seattle, WA, USA 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 and methods: 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. Keywords: adjuvant, lyophilization, tuberculosis, formulation development, design of experiments, controlled temperature chain, GRASKramer RMArcher MCOrr MTDubois Cauwelaert NBeebe EAHuang PWDDowling QMSchwartz AMFedor DMVedvick TSFox CBDove Medical PressarticleAdjuvantLyophilizationTuberculosisFormulation DevelopmentDesign of experimentsControlled temperature chainMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3689-3711 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Adjuvant Lyophilization Tuberculosis Formulation Development Design of experiments Controlled temperature chain Medicine (General) R5-920
spellingShingle	Adjuvant Lyophilization Tuberculosis Formulation Development Design of experiments Controlled temperature chain Medicine (General) R5-920 Kramer RM Archer MC Orr MT Dubois Cauwelaert N Beebe EA Huang PWD Dowling QM Schwartz AM Fedor DM Vedvick TS Fox CB Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
description	Ryan M Kramer, Michelle C Archer, Mark T Orr, Natasha Dubois Cauwelaert, Elyse A Beebe, Po-wei D Huang, Quinton M Dowling, Alicia M Schwartz, Dawn M Fedor, Thomas S Vedvick, Christopher B Fox Infectious Disease Research Institute, Seattle, WA, USA 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 and methods: 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. Keywords: adjuvant, lyophilization, tuberculosis, formulation development, design of experiments, controlled temperature chain, GRAS
format	article
author	Kramer RM Archer MC Orr MT Dubois Cauwelaert N Beebe EA Huang PWD Dowling QM Schwartz AM Fedor DM Vedvick TS Fox CB
author_facet	Kramer RM Archer MC Orr MT Dubois Cauwelaert N Beebe EA Huang PWD Dowling QM Schwartz AM Fedor DM Vedvick TS Fox CB
author_sort	Kramer RM
title	Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
title_short	Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
title_full	Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
title_fullStr	Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
title_full_unstemmed	Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
title_sort	development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/77071a8c5e9b459690ee594b3567806d
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Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach

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