Research in context
Evidence before this study
Most high-income countries now use acellular pertussis vaccines (aPVs) for the prevention of whooping cough or pertussis. However, pertussis outbreaks in highly vaccinated populations have shown the limitations of these vaccines. Rapid waning of vaccine-induced immunity and the failure of aPVs to prevent Bordetella pertussis infection and transmission are prevailing hypotheses for the resurgence of pertussis. B pertussis is a strictly mucosal pathogen, but—unlike natural infection—aPVs do not induce mucosal immunity. Vaccines that mimic natural infection could potentially limit acquisition and accelerate clearance of colonising B pertussis. We searched PubMed with the terms “pertussis”, “whooping cough” AND “mucosal vaccine”, “intranasal”, “live attenuated” for studies of mucosal pertussis vaccination up to July 25, 2022, with no language restriction and in various combinations. Our search yielded 276 references, several of which describe novel mucosal anti-pertussis vaccines. However, none of these novel vaccines have reached clinical development, except for the live attenuated vaccine BPZE1. Two articles detailed safety, colonisation, and serum IgG responses after a nasal administration of a single dose of BPZE1 (containing up to 109 colony-forming units) in phase 1 trials.
Added value of this study
This is the first study of the effect of intranasal BPZE1 vaccination compared with the tetanus–diphtheria–acellular pertussis vaccine (Tdap) vaccine in terms of the induction of nasal secretory IgA response. BPZE1 had an acceptable safety profile and was well tolerated. A single BPZE1 dose induced potent nasal secretory IgA against B pertussis antigens. By contrast, Tdap did not consistently induce secretory IgA responses.
Implications of all the available evidence
This study provides the first proof of concept in humans that a single nasal administration of the live attenuated pertussis vaccine BPZE1 can produce a secretory IgA response against B pertussis. Our findings support further development of BPZE1 as a safe next-generation pertussis vaccine that could potentially reduce B pertussis infection and transmission.