Martinón-Torres, FedericoHalperin, Scott ANolan, TerryTapiéro, BrucePerrett, Kirsten Pde la Cueva, Ignacio SalamancaGarcía-Sicilia, JoséStranak, ZbynekVanderkooi, Otto GKosina, PavelRumlarova, SarkaVirta, MiiaArribas, Jose M MerinoMiranda-Valdivieso, MarianoNovas, Begoña AriasBozensky, JanOrtega, María José CillerueloAmador, Jose Tomas RamosBaca, ManuelPalomino, Esperanza EscribanoZuccotti, Gian VincenzoJanota, JanMarchisio, Paola GiovannaKostanyan, LusineMeyer, NadiaCeregido, Maria AngelesCheuvart, BrigitteKuriyakose, Sherine OMesaros, Narcisa2023-02-092023-02-092021-02-19http://hdl.handle.net/10668/17210Transplacentally 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. 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. 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). 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. ClinicalTrials.gov: NCT02853929.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BluntingBoosterMaternal immunizationPertussisTdap vaccineToddlersAntibodies, BacterialAustraliaCanadaChild, PreschoolDiphtheriaDiphtheria-Tetanus-Pertussis VaccineDiphtheria-Tetanus-acellular Pertussis VaccinesEuropeFemaleFollow-Up StudiesHaemophilus VaccinesHumansImmunityImmunization, SecondaryInfantPoliovirus Vaccine, InactivatedPregnancyTetanusVaccinationVaccines, CombinedWhooping Coughresearch article33612341open access10.1016/j.vaccine.2021.02.0011873-2518https://doi.org/10.1016/j.vaccine.2021.02.001