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

Authors Kramer RM, Archer MC, Orr MT, Dubois Cauwelaert N, Beebe EA, Huang PWD, Dowling QM, Schwartz AM, Fedor DM, Vedvick TS, Fox CB

Received 14 December 2017

Accepted for publication 3 April 2018

Published 26 June 2018 Volume 2018:13 Pages 3689—3711


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

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

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