Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial

Barug, D., Pronk, I., van Houten, M. A., Versteegh, F. G. A., Knol, M. J., van de Kassteele, J., Berbers, G. A. M., Sanders, E. A. M. & Rots, N. Y., Apr-2019, In : Lancet Infectious Diseases. 19, 4, p. 392-401 10 p.

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  • Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands

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  • Daan Barug
  • Inge Pronk
  • Marlies A. van Houten
  • Florens G. A. Versteegh
  • Mirjain J. Knol
  • Jan van de Kassteele
  • Guy A. M. Berbers
  • Elisabeth A. M. Sanders
  • Nynke Y. Rots

Background Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. We investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months.

Methods In an open-label, parallel, randomised, controlled trial, pregnant women aged 18-40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30-32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis-Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1: 1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with (EudraCT 2012-004006-9) and (NTR number NTR4314). The trial is now closed to new participants.

Findings Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16.6, 95% CI 10.9-25.2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all timepoints in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered.

Interpretation In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)392-401
Number of pages10
JournalLancet Infectious Diseases
Issue number4
Publication statusPublished - Apr-2019



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