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

Abstract

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.

Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives

“…In addition to protection in mice, BPZE1 was also shown to be safe and protective against pertussis disease and infection by B. pertussis in non-human primates ( 68 ). The attenuating genetic changes in BPZE1 were shown to be very stable, as evaluated after extensive in vitro and in vivo passaging ( 88 ), and very recently, a lyophilized BPZE1 vaccine formulation was developed and shown to be biologically stable for at least up to 2 years, even when stored at room temperature ( 89 ). BPZE1 is now in clinical development and has successfully completed 2 phase I dose-escalating trials, which showed that the vaccine is safe and immunogenic in adults ( 69 , 70 ).…”

Pasteurian Contributions to the Study of Bordetella pertussis Toxins

“…BPZE1 formulations were optimized as a lyophilized drug product that is stable for at least 2 years at storage temperatures up to room temperature [ 97 ]. It can now be delivered by the use of a spray device after reconstitution.…”

Krztusiec I „Efekt Czerwonej Królowej”

“…W porównaniu ze szczepionką bezkomórkową wywołuje powstawanie przeciwciał o szerszym zakresie działania [40]. Obecnie trwają prace nad otrzymaniem stabilnego preparatu w formie liofilizatu aby można było dopuścić szczepionkę do dalszych badań i komercjalizacji [73].…”