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

Abstract

Background: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.

Methods: 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.

Results: 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.

Conclusions: 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.

Clinical trial registration: ClinicalTrials.gov: NCT02422264.

Keywords: Blunting; Infants; Maternal immunization; Pertussis; Tdap vaccine.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [BAN reports grant from the GSK group of companies (GSK) and personal fees from Pfizer, MSD and Sanofi Pasteur. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC and NMes own GSK restricted shares. FMT, KPP, OGV, SAH and TN’s institutions received grants from GSK during the conduct of the study. FMT’s institution received financial support from GSK during the conduct of the study, as well as financial and non-financial support outside the submitted work; he also received personal fees from Pfizer, Novavax, MSD and Sanofi Pasteur; his institution also received financial support as trial fees from Ablynx, Jansen, Regeneron, Medimmune, Pfizer, MSD, Sanofi Pasteur, Novavax and Novartis, as well as non-financial support from Pfizer and MSD and grants from MSD and AstraZeneca. JMMA reports receiving fees and non-financial support from GSK during the conduct of the study, as well as fees from GSK, Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. SAH is member of ad-hoc advisory committees for GSK and Sanofi Pasteur and he has a patent for novel triple adjuvant issued. ACM, FOT, GVZ, JGS, JTRA, MB, MJCO, MMV, MV, PGM, PM and ZS declare no conflicts of interest.].

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