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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...

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Autores principales: Thalen, Marcel, Debrie, Anne-Sophie, Coutte, Loic, Raze, Dominique, Solovay, Ken, Rubin, Keith, Mielcarek, Nathalie, Locht, Camille
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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