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.