Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution

  1. Christina Vessely1,
  2. Tia Estey1,
  3. Theodore W. Randolph2,
  4. Ian Henderson3,
  5. Julianne Cooper4,
  6. Rajiv Nayar4,
  7. LaToya Jones Braun1,
  8. John F. Carpenter1,*

Article first published online: 4 AUG 2008

DOI: 10.1002/jps.21498

Issue

Journal of Pharmaceutical Sciences

Journal of Pharmaceutical Sciences

Special Issue: Dedicated to Michael J. Pikal

Volume 98, Issue 9, pages 2970–2993, September 2009

Additional Information

How to Cite

Vessely, C., Estey, T., Randolph, T. W., Henderson, I., Cooper, J., Nayar, R., Braun, L. J. and Carpenter, J. F. (2009), Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution. Journal of Pharmaceutical Sciences, 98: 2970–2993. doi: 10.1002/jps.21498

Author Information

  1. 1

    Department of Pharmaceutical Sciences. School of Pharmacy, SOP-215, Campus Box C238, University of Colorado Health Sciences Center, Denver, Colorado 80262

  2. 2

    Department of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, Campus Box 424, University of Colorado, Boulder, Colorado

  3. 3

    DynPort Vaccine Company, LLC, A CSC Company 64 Thomas Johnson Drive, Frederick, Maryland 21702

  4. 4

    HTD Biosystems, 551C Linus Pauling Drive, Hercules, California 94547

*Department of Pharmaceutical Sciences. School of Pharmacy, SOP-215, Campus Box C238, University of Colorado Health Sciences Center, Denver, Colorado 80262. Telephone: 303-315-6075; Fax: 303-315-6281.

Publication History

  1. Issue published online: 27 JUL 2009
  2. Article first published online: 4 AUG 2008
  3. Manuscript Accepted: 28 MAY 2008
  4. Manuscript Revised: 14 MAY 2008
  5. Manuscript Received: 27 FEB 2008

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Keywords:

  • botulinum neurotoxin;
  • recombinant vaccine;
  • trivalent vaccine;
  • stability;
  • aluminum salt adjuvant;
  • competitive adsorption

Abstract

The adsorption of recombinant botulinum neurotoxin (BoNT) protein-derived vaccine antigens to aluminum salt adjuvants has been previously studied for the development of a trivalent vaccine against the neurotoxins (Vessely et al., in press, J Pharm Sci). The current paper describes an investigation of the stability of recombinant BoNT antigens adsorbed to aluminum salt adjuvants during storage in aqueous solution. Both chemical and physical changes occurred during storage. Phosphate groups in the buffer exchanged with hydroxyl groups on the adjuvant surface. The resulting changes in solution pH and adjuvant surface chemistry promoted more favorable electrostatic interaction between the BoNT proteins and the surface, possibly increasing the affinity of the proteins for the surface during storage. Fluorescence and UV spectroscopy suggested changes to protein structure during storage, whereas differential scanning calorimetry showed changes to thermal processes related to protein conformation and/or surface adsorption. The consequence of the chemical and physical changes to the proteins was a decrease in the ability to desorb protein from the adjuvant surface during storage. Overall, the results of this study emphasize the utility of a thorough characterization of the interactions between protein antigens and aluminum salt adjuvants. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2970–2993, 2009

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