Boosting Teenagers With Acellular Pertussis Vaccines Containing Recombinant or Chemically Inactivated Pertussis Toxin: A Randomized Clinical Trial.

Autor:	Blanchard Rohner G; Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva.; Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland., Chatzis O; Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva.; Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland., Chinwangso P; BioNet-Asia Co, Ltd, Bangkok, Thailand., Rohr M; Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva.; Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland., Grillet S; Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland., Salomon C; Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva., Lemaître B; Laboratory of Vaccinology, University Hospitals of Geneva, Switzerland., Boonrak P; Center of Excellence for Biomedical and Public Health Informatics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Lawpoolsri S; Center of Excellence for Biomedical and Public Health Informatics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Clutterbuck E; Oxford Vaccine Group, Department of Paediatrics, University of Oxford.; National Institute for Health Research Oxford Biomedical Research Centre, United Kingdom., Poredi IK; BioNet-Asia Co, Ltd, Bangkok, Thailand., Wijagkanalan W; BioNet-Asia Co, Ltd, Bangkok, Thailand., Spiegel J; BioNet-Asia Co, Ltd, Bangkok, Thailand., Pham HT; BioNet-Asia Co, Ltd, Bangkok, Thailand., Viviani S; BioNet-Asia Co, Ltd, Bangkok, Thailand., Siegrist CA; Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva.; Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2019 Mar 19; Vol. 68 (7), pp. 1213-1222.
DOI:	10.1093/cid/ciy594
Abstrakt:	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. (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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