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Pharmaceutical Research

, 37:11 | Cite as

Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine

  • Dominique N. Price
  • Nitesh K. Kunda
  • Rajaun Ellis
  • Pavan MuttilEmail author
Research Paper

Abstract

Purpose

Loss of vaccine potency due to extreme temperature exposure during storage and transport remains a significant obstacle to the success of many vaccines, including the Bacille Calmette-Guérin (BCG) vaccine, the only vaccine available against Mycobacterium tuberculosis. BCG is a live, attenuated vaccine requiring refrigerated storage for viability. In this study, we formulated a temperature-stable BCG dry powder using the spray drying technique.

Methods

We employed a factorial design to optimize our formulation of stabilizing excipients that included L-leucine, bovine serum albumin, polyvinylpyrrolidone, mannitol, and trehalose. Powders were characterized for their particle size, yield, water retention and uptake, glass transition temperature, and aerosol performance. Three optimal powder carrier mixtures were selected from the factorial design for BCG incorporation based on their stability-promoting and powder flow characteristics. Vaccine powders were also assessed for BCG viability and in vivo immunogenicity after long-term storage.

Results

Live BCG was successfully spray-dried using the optimized carriers. Dry powder BCG showed no loss in viability (25°C, up to 60% relative humidity; RH) and ~2-log loss in viability (40°C, 75% RH) after one year of storage. The aerodynamic size of the powders was in the respirable range. Further, when healthy mice were immunized intradermally with reconstituted BCG powders (storage for 2 years), the vaccine retained its immunogenicity.

Conclusion

We developed a spray-dried BCG vaccine that was viable and antigenic after long-term storage. To our knowledge, this is a first study to show room temperature stability of live BCG vaccine without any loss in viability for 12 months.

Key Words

BCG cold-chain factorial design live bacterial vaccine pulmonary vaccination spray drying tuberculosis vaccine formulation vaccine stability 

Notes

Acknowledgements and Disclosure

The authors would like to acknowledge Dr. Avni Patel for her help with the initial spray drying experiments. Laura Stephens for her help with the phagocytosis assay. We would also like to thank Dr. Hien Pham for the use of SEM, Dr. Eric Peterson for XRD, and Dr. Stephen Jett for TEM analysis.The authors declare no conflict of interest.

Funding

This work was funded in part by the Bill and Melinda Gates Grand Challenges Exploration (OPP1061393; PI- Dr. Pavan Muttil), National Institute of Allergy and Infectious Diseases (T32 Training Grant No: A1007538; Recipient- DNP), and by the National Research Foundation (Grant# 105830, South Africa; PI- Dr. Bernard Fourie).

Supplementary material

11095_2019_2739_MOESM1_ESM.docx (504 kb)
ESM 1 (DOCX 504 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dominique N. Price
    • 1
    • 2
  • Nitesh K. Kunda
    • 1
    • 3
  • Rajaun Ellis
    • 4
    • 5
  • Pavan Muttil
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of New Mexico, Health Sciences CenterAlbuquerqueUSA
  2. 2.Biomedical Sciences Graduate ProgramUniversity of New Mexico, Health Sciences CenterAlbuquerqueUSA
  3. 3.Department of Pharmaceutical Sciences, College of Pharmacy and Health SciencesSt. John’s UniversityJamaicaUSA
  4. 4.Health Sciences CenterUniversity of New MexicoAlbuquerqueUSA
  5. 5.Nova Southeastern UniversityFort LauderdaleUSA

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