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Observational Study
. 2019 Jul;197(1):1-10.
doi: 10.1111/cei.13275. Epub 2019 Mar 13.

Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy - a prospective, observational cohort study from the United Kingdom

T F Rice  1 , D A Diavatopoulos  2   3 , G P Smits  4 , P G M van Gageldonk  4 , G A M Berbers  4 , F R van der Klis  4 , G Vamvakas  5 , B Donaldson  1 , M Bouqueau  1 , B Holder  1 , B Kampmann  1   6   7
Affiliations
Observational Study

Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy - a prospective, observational cohort study from the United Kingdom

T F Rice et al. Clin Exp Immunol. 2019 Jul.

Abstract

The maternal Tdap (tetanus, diphtheria and acellular pertussis) vaccination programme in the United Kingdom has successfully reduced cases of pertussis in young infants. In addition to prevention of pertussis cases, it is also important to investigate the persistence of maternal antibodies during infancy and the possible interference of maternal antibodies with infant responses to vaccines. We recruited mother-infant pairs from vaccinated and unvaccinated pregnancies and measured concentrations of immunoglobulin (Ig)G against pertussis toxin (PTx), filamentous haemagglutinin (FHA), pertactin (Prn), diphtheria toxin (DTx), tetanus toxoid (TTx) Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae in mothers and infants at birth, and in infants at 7 weeks and at 5 months. Thirty-one mother-infant pairs were tested. Tdap-vaccinated women had significantly higher antibody against Tdap antigens, compared to unvaccinated women (DTx, P = 0·01; PTx, FHA, Prn and TTx, P < 0·001). All antibodies were actively transferred to the infants (transfer ratio > 1) with higher transfer of DTx (P = 0·04) and TTx (P = 0·02) antibody in Tdap-vaccinated pregnancies compared to unvaccinated pregnancies. Infants from Tdap-vaccinated pregnancies had significantly elevated antibodies to all antigens at birth (P < 0.001) and at 7 weeks (FHA, Prn, TTx, P < 0·001; DTx, P = 0.01; PTx, P = 0·004) compared to infants from unvaccinated pregnancies. Infants from Tdap-vaccinated and -unvaccinated pregnancies had comparable antibody concentrations following primary pertussis immunization (PTx, P = 0·77; FHA, P = 0·58; Prn, P = 0·60; DTx, P = 0·09; TTx, P = 0·88). These results support maternal immunization as a method of protecting vulnerable infants during their first weeks of life.

Keywords: antibodies; human; reproductive immunology; vaccination.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Anti‐tetanus, diphtheria and acellular pertussis (Tdap) antibody concentrations in mothers and their infants from Tdap‐vaccinated and ‐unvaccinated pregnancies (a–e). The proportion of infants from Tdap‐vaccinated and ‐unvaccinated pregnancies reaching antibody thresholds (f–j). (a–e) Anti‐Tdap immunoglobulin (Ig)G were quantified in mother–infant pairs from vaccinated (white circle) and unvaccinated (black circle) pregnancies. Data were log‐transformed, and a random‐effects model applied. Mean and 95% confidence intervals are shown. The vaccinated group had significantly elevated antibodies to (a) PTx, (b) FHA, (c) Prn, (d) Dtx and (e) TTx vaccine antigens in mothers at birth, in cord blood and in the infant prevaccination (pre‐vac; 7 weeks of age). Post‐infant vaccination (post‐vac; 5 months of age), there were no significant differences in antibody to any of the vaccine antigens between vaccinated and unvaccinated groups (*P < 0·05; ***P < 0·001; ****P < 0·0001; unvaccinated n = 15; vaccinated n = 16). (f–j) Cut‐offs were set at ≥20 IU/ml for pertussis antigens and ≥0·1 IU/ml for DTx and TTx. The proportion of infants at birth, 7 weeks and 5 months that reached these cut‐offs is represented as a percentage of total samples analysed in vaccinated (solid line) and unvaccinated (dashed line) groups. At birth and 7 weeks, the percentage of infants reaching seropositive levels for PTx, FHA, Prn and DTx was significantly higher in the group born to Tdap‐vaccinated mothers than those born to non‐vaccinated mothers. There was no difference for TTx. Post‐primary immunization, there was no difference between the two groups (**P < 0·01; ***P < 0·001; ****P < 0·0001).
Figure 2
Figure 2
Longitudinal pneumococcal and Haemophilus influenzae (Hib) antibody concentrations in mothers and their infants from maternal tetanus, diphtheria and acellular pertussis (Tdap) vaccinated and unvaccinated pregnancies. Immunoglobulin (Ig)G against pneumococcal serotypes (Ps) and Hib were quantified in mother–infant pairs from vaccinated (white circles) and unvaccinated (black circles) pregnancies. Data were log‐transformed, and a random‐effects model applied. Mean and 95% confidence intervals are shown. No differences were observed in antibody to serotypes (a) 1, (b) 4, (c) 5, (d) 6B, (e) 7F, (f) 9V, (g) 14, (h) 18C, (i) 19F, (j) 23F in mothers during pregnancy and at birth, or in cord blood and the infant prevaccination (pre‐vac; 7 weeks of age). Post‐vaccination (post‐vac; 5 months of age), infants from vaccinated pregnancies had elevated serotype 14, whereas infants from the unvaccinated group had elevated 7F. (k) Hib antibody did not differ between vaccinated and unvaccinated groups at any study time‐points (*P < 0·05; **P < 0·01; unvaccinated n = 15; vaccinated n = 16).
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