Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial.

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. 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.

Martinón-Torres F ，Halperin SA ，Nolan T ，Tapiéro B ，Perrett KP ，de la Cueva IS ，García-Sicilia J ，Stranak Z ，Vanderkooi OG ，Kosina P ，Rumlarova S ，Virta M ，Arribas JMM ，Miranda-Valdivieso M ，Novas BA ，Bozensky J ，Ortega MJC ，Amador JTR ，Baca M ，Palomino EE ，Zuccotti GV ，Janota J ，Marchisio PG ，Kostanyan L ，Meyer N ，Ceregido MA ，Cheuvart B ，Kuriyakose SO ，Mesaros N ... -  《-》

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial.

Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7-366/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. ClinicalTrials.gov: NCT02422264.

Perrett KP ，Halperin SA ，Nolan T ，Carmona Martínez A ，Martinón-Torres F ，García-Sicilia J ，Virta M ，Vanderkooi OG ，Zuccotti GV ，Manzoni P ，Kostanyan L ，Meyer N ，Ceregido MA ，Cheuvart B ，Kuriyakose SO ，Stranak Z ，Merino Arribas JM ，Cilleruelo Ortega MJ ，Miranda-Valdivieso M ，Arias Novas B ，Ramos Amador JT ，Omeñaca F ，Baca M ，Marchisio PG ，Mesaros N ... -  《-》

Immunogenicity and safety following primary and booster vaccination with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine: a randomized trial in the United States.

Klein NP ，Abu-Elyazeed R ，Cheuvart B ，Janssens W ，Mesaros N ... -  《-》

Safety and immunogenicity of a toddler dose following an infant series of a hexavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b, hepatitis B vaccine administered concurrently or at separate visits wit

Halperin SA ，Tapiéro B ，Dionne M ，Meekison W ，Diaz-Mitoma F ，Zickler P ，Rubin E ，Embree J ，Bhuyan P ，Lee A ，Li M ，Tomovici A ... -  《-》

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Wanlapakorn N ，Sarawanangkoor N ，Srimuan D ，Thatsanathorn T ，Thongmee T ，Poovorawan Y ... -  《-》