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Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine.
Pharm Res. 2019 Dec 23; 37(1):11.PR

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Health Sciences Center, Albuquerque, New Mexico, 87131, USA. Biomedical Sciences Graduate Program, University of New Mexico, Health Sciences Center, Albuquerque, New Mexico, 87131, USA.Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Health Sciences Center, Albuquerque, New Mexico, 87131, USA. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York, 11439, USA.Health Sciences Center, University of New Mexico, Albuquerque, New Mexico, 87131, USA. Nova Southeastern University, Fort Lauderdale, Florida, 33314, USA.Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Health Sciences Center, Albuquerque, New Mexico, 87131, USA. pmuttil@salud.unm.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31873825

Citation

Price, Dominique N., et al. "Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine." Pharmaceutical Research, vol. 37, no. 1, 2019, p. 11.
Price DN, Kunda NK, Ellis R, et al. Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine. Pharm Res. 2019;37(1):11.
Price, D. N., Kunda, N. K., Ellis, R., & Muttil, P. (2019). Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine. Pharmaceutical Research, 37(1), 11. https://doi.org/10.1007/s11095-019-2739-8
Price DN, et al. Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine. Pharm Res. 2019 Dec 23;37(1):11. PubMed PMID: 31873825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine. AU - Price,Dominique N, AU - Kunda,Nitesh K, AU - Ellis,Rajaun, AU - Muttil,Pavan, Y1 - 2019/12/23/ PY - 2019/09/20/received PY - 2019/11/24/accepted PY - 2019/12/25/entrez PY - 2019/12/25/pubmed PY - 2020/2/28/medline KW - BCG KW - cold-chain KW - factorial design KW - live bacterial vaccine KW - pulmonary vaccination KW - spray drying KW - tuberculosis KW - vaccine formulation KW - vaccine stability SP - 11 EP - 11 JF - Pharmaceutical research JO - Pharm. Res. VL - 37 IS - 1 N2 - 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. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/31873825/Design_and_Optimization_of_a_Temperature_Stable_Dry_Powder_BCG_Vaccine_ L2 - https://doi.org/10.1007/s11095-019-2739-8 DB - PRIME DP - Unbound Medicine ER -