BACKGROUND: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. METHODS: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7-366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. RESULTS: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). CONCLUSIONS: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02853929.

Alberta Children's Hospital University of Calgary Departments of Pediatrics Microbiology Immunology and Infectious Diseases Pathology and Laboratory Medicine and Community Health Sciences Alberta Children's Hospital Research Institute Alberta Calgary AB T3B 6A8 Canada

CHU Sainte Justine Université de Montréal Montréal QC H3T 1C5 Canada

Dalhousie University Canadian Center for Vaccinology Halifax NS B3K 6R8 Canada

Departamento de Salud Pública y Materno Infantil Hospital Clínico San Carlos 28040 Madrid Spain

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico 20122 Milan Italy; Università degli Studi di Milano 20122 Milan Italy

GSK Vaccines 1300 Wavre Belgium

GSK Vaccines Bangalore 560001 India

Hospital Clínico Universitario de Santiago Pediatría Clínica Infectológica y Traslacional 15706 Santiago de Compostela Spain; Genetics Vaccines and Pediatrics Research Group University of Santiago de Compostela Instituto de Investigación Sanitaria de Santiago de Compostela 15706 Santiago de Compostela Spain

Hospital de Antequera Servicio de Pediatría 29200 Antequera Spain

Hospital Quiron Malaga Departamento de Pediatría y Neonatología 29004 Malaga Spain

Hospital Universitario La Paz Servicio de Neonatologia 28046 Madrid Spain

Hospital Universitario Madrid Sanchinarro Servicio de Pediatría 28050 Madrid Spain

Hospital Universitario Puerta de Hierro Majadahonda Servicio de Pediatría 28222 Madrid Spain

Hospital Universitario Sanitas La Zarzuela Servicio de Pediatría 28023 Aravaca Spain

Institute for the Care of Mother and Child Neonatology Department 147 00 Prague Czech Republic

Instituto Hispalense de Pediatría Unidad de Investigación 41014 Seville Spain

Murdoch Children's Research Institute and the Melbourne School of Population and Global Health at The University of Melbourne Melbourne VIC 3052 Australia

Nuevo Hospital Universitario de Burgos Departamento de Pediatría 09006 Burgos Spain

Ospedale dei Bambini Vittore Buzzi and University of Milan 20154 Milan Italy

Tampere Vaccine Research Center Tampere University 33100 Tampere Finland

Thomayer Hospital Prague Department of Neonatology 140 59 Prague Czech Republic

University Hospital Department of Infectious Diseases 500 05 Hradec Kralove Czech Republic

Vitkovice Hospital Pediatrics Department 703 00 Ostrava Czech Republic

Citace poskytuje Crossref.org

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ClinicalTrials.gov
NCT02853929