Journal Article

Boosting Teenagers With Acellular Pertussis Vaccines Containing Recombinant or Chemically Inactivated Pertussis Toxin

Spiegel, Jane, Boonrak, Pitchaya, Clutterbuck, Elizabeth, Lemaître, Barbara, Pham, Hong Thai, Grillet, Stéphane, Rohner, Geraldine Blanchard, Chatzis, Olga, Wijagkanalan, Wassana, Salomon, Carole, Lawpoolsri, Saranath, Siegrist, Claire-Anne, Poredi, Indrajeet Kumar, Chinwangso, Pailinrut, Rohr, Marie, Viviani, Simonetta

2019

Overview

Abstract Background Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. Methods We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed. Results Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88–109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73–168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41–75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31–146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting. Conclusions Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects. Clinical Trials Registration NCT02946190. We compared recombinant vs chemically detoxified pertussis toxin (PT)–containing vaccines in adolescents primed with 5 doses of acellular pertussis vaccines. Recombinant PT was safe and significantly more immunogenic, and reactivated more memory B cells than the comparator licensed vaccine.

• Publisher: Oxford University Press
• Subject: Adhesins, Bacterial - genetics / Adhesins, Bacterial - immunology / Adolescent / Antibodies, Bacterial - blood / Antibodies, Neutralizing - blood / Antitoxins - blood / ARTICLES AND COMMENTARIES / B-Lymphocyte Subsets - immunology / Child / Female / Humans / Immunization, Secondary - methods / Immunologic Memory / Male / Pertussis Toxin - genetics / Pertussis Toxin - immunology / Pertussis Vaccine - administration & dosage / Pertussis Vaccine - immunology / Switzerland / Vaccines, Acellular - administration & dosage / Vaccines, Acellular - immunology / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - immunology / Virulence Factors, Bordetella - genetics / Virulence Factors, Bordetella - immunology / Whooping Cough - prevention & control