The potential public health benefit of live-attenuated pertussis vaccines

Despite high vaccination coverage, pertussis remains endemic, and epidemic cycles continue to occur every 3-5 years, illustrating the shortcomings of current vaccination strategies. Unlike current vaccines, especially acellular pertussis vaccines, which prevent disease for short duration but do not prevent nasal colonization by the etiological agent Bordetella pertussis, natural infection can induce durable immunity against disease and infection. Accordingly, live-attenuated nasal pertussis vaccine candidates have been developed to mimic the immunogenicity of natural infection without causing disease.

We summarize the current status of live-attenuated nasal pertussis vaccines based on a literature search with keywords 'pertussis vaccine,' 'live,' and 'attenuated.' These candidates were designed based on different strategies, including dependence on critical metabolites for bacterial growth, genetic attenuation of virulence, and modification of immunomodulatory properties of Bordetella.

Only vaccines based on genetic attenuation of virulence have reached clinical development thus far. The most advanced candidate is BPZE1, which has successfully completed six clinical studies, demonstrating safety, systemic and mucosal immunogenicity, and the ability to prevent or substantially reduce B. pertussis infection. If BPZE1 is eventually adopted for global use, it will likely be a major breakthrough in the ultimate control of pertussis, which has plagued humanity for centuries.