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-blind
Peer reviewers approved by Dr Farooq Shiekh
Peer reviewer comments 2
Editor who approved publication: Dr Thomas J 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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