Efficacy, immunogenicity, and safety of the live attenuated nasal pertussis vaccine, BPZE1, in the UK: a randomised, placebo-controlled, phase 2b trial using a controlled human infection model with virulent Bordetella pertussis.

Summary

In this randomized, placebo-controlled human challenge trial, BPZE1 prevented or substantially reduced colonization by virulent Bordetella pertussis. In the per-protocol adequate inoculum population, 60% of BPZE1 recipients versus 25% of placebo had no detectable colonization on days 9, 11, and 14 post-challenge (p=0.033). Safety was favorable with mostly mild local/systemic events and no serious adverse events.

Key Findings

• Per-protocol adequate inoculum: 60% (12/20) BPZE1 vs 25% (4/16) placebo had no detectable colonization on days 9, 11, and 14 (p=0.033).
• Modified ITT trend favored BPZE1 (58% vs 33% with no detectable colonization; p=0.091).
• Reactogenicity was mostly mild; no serious adverse events or discontinuations due to adverse events.

Clinical Implications

If validated in larger phase 3 studies, BPZE1 could complement or replace current pertussis strategies by reducing carriage and transmission, potentially reshaping outbreak control and infant protection through herd effects.

Limitations

• Small sample size with limited generalizability (healthy adults 18–50 years).
• Short follow-up focusing on colonization (not clinical disease) and some participants received lower-than-target challenge dose.

Future Directions

Phase 3 trials in broader populations (including adolescents and pregnant women) assessing durability, transmission impact, and effectiveness against clinical disease; immunologic correlates of protection.