Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1

Vaccines

Dominique Raze¹  Nathalie Mielcarek¹  Anne-Sophie Debrie¹  Loic Coutte¹  Camille Locht¹  Marcel Thalen²  Keith Rubin²  Ken Solovay² 

[1] Centre d’Infection et d’Immunité de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, U1019–UMR9017–CIIL–Center for Infection and Immunity of Lille, F-59000 Lille, France;ILiAD Biotechnologies, New York, NY 10003, USA;

关键词: pertussis;    live attenuated vaccine;    lyophilization;    vaccine stability;   

DOI  :  10.3390/vaccines8030523

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown