Safety and immunogenicity of a genetically inactivated stand-alone acellular pertussis vaccine as a booster to Australian adults: a randomized, controlled, non-inferiority trial

Introduction Waning immunity after acellular pertussis (aP) vaccines shown in pertussis outbreaks highlights the need for more effective aP vaccines. We evaluated the immunogenicity and safety of a stand-alone 2-component aP vaccine (aP 2 ) containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) compared with a licensed 3-component Tdap vaccine (Tdap 3 ) containing chemically inactivated PT, FHA, and pertactin (PRN) in adults. Methods This randomized controlled trial enrolled 102 healthy Australian adults aged 18–30 years. Participants were randomized 2:1 (aP 2 : Tdap 3 ) with stratification for priming in infancy with whole-cell (wP) or aP vaccines. Immunogenicity was assessed measuring serum PT-IgG, FHA-IgG and PT-neutralizing antibodies (PTNA) at baseline, Day-28 and 1-year post-vaccination. Seroconversion was defined as ≥4-fold rise in antibody titers from baseline. Safety was monitored throughout. Results Day 28 seroconversion rates for PT-IgG were 98.5% (95% CI 91.7–100.0) for aP 2 and 82.4% (65.5–93.2) for Tdap 3 (Δ, absolute difference = 16.1%) and for FHA-IgG 87.7% (77.2–94.5) for aP 2 and 61.8% (43.6–77.8) for Tdap 3 (Δ25.9%), meeting the pre-defined seroconversion non-inferiority margin of > − 10%. Geometric mean concentrations/titers of PT-IgG and PTNA were significantly higherin the aP 2 group compared to Tdap 3 at 28 days (PT-IgG 132.70 IU/mL vs. 57.42 IU/mL, p = 0.0001; PTNA 146.97 IU/mL vs. 69.32 IU/mL, p = 0.0010) and 1-year post-vaccination (PT-IgG 27.61 IU/mL vs. 12.51 IU/mL, p = 0.0099; PTNA 31.02 IU/mL vs. 15.70 IU/mL, p = 0.0100). Exploratory analysis showed aP 2 elicited higher PT-IgG and PTNA titers in both wP- and aP-primed adults at both timepoints. Safety profiles were comparable between vaccines, with most adverse events being mild to moderate. Four serious adverse events were reported throughout the study, none of which were vaccine-related. Conclusion These findings suggest that aP 2 vaccine is safe and more immunogenic in adults compared with Tdap 3 vaccine, supporting its use as a pertussis booster.