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Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1
Current pertussis vaccines protect against disease, but not against colonization by and transmission of Bordetella pertussis, whereas natural infection protects against both. The live attenuated vaccine BPZE1 was developed to mimic immunogenicity of natural infection without causing disease, and in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565209/ https://www.ncbi.nlm.nih.gov/pubmed/32933132 http://dx.doi.org/10.3390/vaccines8030523 |
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author | Thalen, Marcel Debrie, Anne-Sophie Coutte, Loic Raze, Dominique Solovay, Ken Rubin, Keith Mielcarek, Nathalie Locht, Camille |
author_facet | Thalen, Marcel Debrie, Anne-Sophie Coutte, Loic Raze, Dominique Solovay, Ken Rubin, Keith Mielcarek, Nathalie Locht, Camille |
author_sort | Thalen, Marcel |
collection | PubMed |
description | Current pertussis vaccines protect against disease, but not against colonization by and transmission of Bordetella pertussis, whereas natural infection protects against both. The live attenuated vaccine BPZE1 was developed to mimic immunogenicity of natural infection without causing disease, and in preclinical models protected against pertussis disease and B. pertussis colonization after a single nasal administration. Phase 1 clinical studies showed that BPZE1 is safe and immunogenic in humans when administered as a liquid formulation, stored at ≤−70 °C. Although BPZE1 is stable for two years at ≤−70 °C, a lyophilized formulation stored at ≥5 °C is required for commercialization. The development of a BPZE1 drug product, filled and lyophilized directly in vials, showed that post-lyophilization survival of BPZE1 depended on the time of harvest, the lyophilization buffer, the time between harvest and lyophilization, as well as the lyophilization cycle. The animal component-free process, well defined in terms of harvest, processing and lyophilization, resulted in approximately 20% survival post-lyophilization. The resulting lyophilized drug product was stable for at least two years at −20 °C ± 10 °C, 5 °C ± 3 °C and 22.5 °C ± 2.5 °C and maintained its vaccine potency, as evaluated in a murine protection assay. This manufacturing process thus enables further clinical and commercial development of BPZE1. |
format | Online Article Text |
id | pubmed-7565209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75652092020-10-26 Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 Thalen, Marcel Debrie, Anne-Sophie Coutte, Loic Raze, Dominique Solovay, Ken Rubin, Keith Mielcarek, Nathalie Locht, Camille Vaccines (Basel) Article Current pertussis vaccines protect against disease, but not against colonization by and transmission of Bordetella pertussis, whereas natural infection protects against both. The live attenuated vaccine BPZE1 was developed to mimic immunogenicity of natural infection without causing disease, and in preclinical models protected against pertussis disease and B. pertussis colonization after a single nasal administration. Phase 1 clinical studies showed that BPZE1 is safe and immunogenic in humans when administered as a liquid formulation, stored at ≤−70 °C. Although BPZE1 is stable for two years at ≤−70 °C, a lyophilized formulation stored at ≥5 °C is required for commercialization. The development of a BPZE1 drug product, filled and lyophilized directly in vials, showed that post-lyophilization survival of BPZE1 depended on the time of harvest, the lyophilization buffer, the time between harvest and lyophilization, as well as the lyophilization cycle. The animal component-free process, well defined in terms of harvest, processing and lyophilization, resulted in approximately 20% survival post-lyophilization. The resulting lyophilized drug product was stable for at least two years at −20 °C ± 10 °C, 5 °C ± 3 °C and 22.5 °C ± 2.5 °C and maintained its vaccine potency, as evaluated in a murine protection assay. This manufacturing process thus enables further clinical and commercial development of BPZE1. MDPI 2020-09-13 /pmc/articles/PMC7565209/ /pubmed/32933132 http://dx.doi.org/10.3390/vaccines8030523 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Thalen, Marcel Debrie, Anne-Sophie Coutte, Loic Raze, Dominique Solovay, Ken Rubin, Keith Mielcarek, Nathalie Locht, Camille Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title | Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title_full | Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title_fullStr | Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title_full_unstemmed | Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title_short | Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1 |
title_sort | manufacture of a stable lyophilized formulation of the live attenuated pertussis vaccine bpze1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565209/ https://www.ncbi.nlm.nih.gov/pubmed/32933132 http://dx.doi.org/10.3390/vaccines8030523 |
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