Pertussis toxin (PT), particularly if genetically detoxified (PT_gen), represents the main antigen ensuring protection from pertussis disease.³ We previously demonstrated⁴ that recombinant acellular pertussis vaccines containing PT_gen are more immunogenic and induce significantly higher PT-neutralizing antibody titers in adolescents than chemically inactivated tetanus-diphtheria-pertussis booster vaccines (Tdap_chem). Follow-up studies have found that anti-PT antibodies remained greater than prevaccination levels 3 years after booster vaccination with recombinant pertussis vaccine, unlike with Tdap_chem.⁵ We now report on antibody persistence 5 years after recombinant pertussis booster vaccination.

Methods

The eMethods in Supplement 1 includes detailed methods. The present cohort study was a follow-up of participants who were vaccinated 5 years earlier, when aged 12 to 17 years, with recombinant acellular pertussis vaccine containing 5 μg of PT_gen and 5 μg of filamentous hemagglutinin (FHA) in a pertussis-only formulation (aP_gen) or a combined tetanus-diphtheria-pertussis formulation (TdaP_gen) compared with those vaccinated with Tdap_chem containing 2.5 μg of chemically detoxified PT, 5 μg of FHA, 3 μg of pertactin, and 5 μg Fimbriae types 2 and 3 during a phase 2/3 randomized clinical trial conducted between July 2015 and November 2016 in Thailand.⁴ Study participants were reconsented for participation in the 5-year follow-up study. Written informed consent was obtained from participants aged 18 years and older and from both participants younger than 18 years and their parents or legal guardians cosigned prior to study entry. Ethical approval was obtained from the ethics committee of the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. The study is registered at Clinicaltrials.gov (NCT04529720). STROBE reporting guidelines for cohort studies were followed.

Participants had been primed with 3 doses of whole-cell pertussis vaccine in infancy. Earlier follow-ups were conducted at 2 and 3 years after booster vaccination and have been reported previously.⁵ To be eligible, participants had to have completed the original trial at 1-year postvaccination at the Vaccine Trial Centre, Mahidol University, Bangkok, Thailand (1 of 2 study sites) and were not to have received pertussis vaccine since the study booster 5 years earlier. A blood sample was collected, and serum PT-IgG and FHA-IgG concentrations in all participants and PT neutralizing antibody titers in a subset (aP_gen, 21 participants; TdaP_gen, 15 participants; and TdaP_chem, 19 participants) were analyzed using validated in-house ELISA and Chinese Hamster Ovary assays calibrated against the WHO International Standard Pertussis Antiserum (Human) 06/140.^4,5 Geometric mean concentrations (GMCs) or geometric mean titers (GMTs), ratios compared with prebooster GMCs and GMTs, seropositivity rates (>5 IU/mL), proportions of participants with long-term booster responses (>20 IU/mL), and 95% CIs were calculated. Statistical analysis was conducted in SAS version 9.4 (SAS Institute), and P < .05 indicated statistical significance.

Of 223 eligible participants, 159 (71%) were screened and enrolled, with 55 receiving aP_gen; 52, TdaP_gen; and 52, Tdap_chem. The mean (SD) age was 19.6 (1.8) years (range, 17-23 years), and 56% of participants were female. There were no differences between groups. Five years after booster vaccination with recombinant pertussis vaccine, anti-PT antibodies remained significantly elevated (Table), with PT neutralizing antibodies persisting at 2.5-fold (aP_gen) and 3.0-fold (TdaP_gen) higher levels than prevaccination (Figure). PT-IgG antibodies persisted at levels greater than 20 IU/mL in 75% of aP_gen vaccinees (41 of 55 participants) and 56% of TdaP_gen vaccinees (29 of 52 participants) compared with 27% of Tdap_chem vaccinees (14 of 52 participants) (P < .001) (Table).

This study illustrates the sustained persistence of immunity 5 years after booster vaccination with recombinant acellular pertussis vaccines. The 5-year persistence of neutralizing anti-PT antibodies at levels more than 4-fold greater than the seropositivity cutoff of 5 IU/mL supports the capacity of recombinant pertussis vaccines to boost long-lasting protection. The modest decline in neutralizing antibody levels between 2 and 5 years after vaccination suggests that protective immunity may persist well beyond 5 years.

Long-lasting protection was demonstrated earlier in an efficacy trial for PT_gen-containing recombinant vaccines after primary immunization in infants.⁶ Our findings suggest that PT_gen-containing vaccines can also offer longer-lasting protection in adolescents, supporting their use as booster vaccines in adolescents and adults to enhance population immunity. However, effectiveness studies are needed to demonstrate the clinical impact of the immunological observations.

Source: Jama Network Open