Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial. Issue 11 (12th March 2021)

• Record Type: Journal Article
• Authors: Martinón-Torres, Federico; Halperin, Scott A.; Nolan, Terry; Tapiéro, Bruce; Perrett, Kirsten P.; de la Cueva, Ignacio Salamanca; García-Sicilia, José; Stranak, Zbynek; Vanderkooi, Otto G.; Kosina, Pavel; Rumlarova, Sarka; Virta, Miia; Arribas, Jose M. Merino; Miranda-Valdivieso, Mariano; Novas, Begoña Arias; Bozensky, Jan; Ortega, María José Cilleruelo; Amador, Jose Tomas Ramos; Baca, Manuel; Palomino, Esperanza Escribano; Zuccotti, Gian Vincenzo; Janota, Jan; Marchisio, Paola Giovanna; Kostanyan, Lusine; Meyer, Nadia; Ceregido, Maria Angeles; Cheuvart, Brigitte; Kuriyakose, Sherine O.; Mesaros, Narcisa
• Is Part Of: Vaccine. Volume 39:Issue 11(2021)
• Page Start: 1598
• Page End: 1608
• Publication Date: 2021-03-12
• Subjects: Tdap vaccine -- Pertussis -- Maternal immunization -- Blunting -- Toddlers -- Booster; AE adverse event -- ATP according-to-protocol -- CI confidence interval -- CPS capsular polysaccharide -- DTaP-HepB-IPV/Hib diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine -- DU D antigen units -- ECL electrochemiluminescence -- ELISA enzyme-linked immunosorbent assay -- FHA filamentous hemagglutinin -- GMC geometric mean concentration -- GMT geometric mean titer -- HBs hepatitis B surface antigen -- Hib Haemophilus influenzae type b -- IPV inactivated poliovirus -- IU international units -- PCV13 13-valent pneumococcal conjugate vaccine -- PRN pertactin -- PRP polyribosylribitol phosphate -- PT pertussis toxoid -- SAE serious adverse event -- Tdap tetanus-reduced-antigen-content diphtheria-acellular pertussis vaccine -- TT tetanus toxoid -- TVC total vaccinated cohort -- UK United Kingdom -- US United States -- WHO World Health Organization; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.02.001
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Toddlers in a randomized maternal Tdap immunization trial received a DTaP-HepB-IPV/Hib booster. Response to pertussis and to other antigens were similarly high in toddlers from vaccinated and unvaccinated mothers. Antibody concentrations for two pertussis antigens and diphtheria were lower in toddlers from vaccinated mothers. The clinical significance of this immune interference needs long-term monitoring. Abstract: 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 27 0/7 –36 6/7 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.