Dataset Information

The Effect of Tetanus-Diphtheria-Acellular-Pertussis Immunization During Pregnancy on Infant Antibody Responses: Individual-Participant Data Meta-Analysis.

ABSTRACT:

Background

Immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in pregnancy is increasingly recommended. We determined the effect of Tdap immunization in pregnancy on infants' vaccine responses.

Methods

Individual-participant data meta-analysis of ten studies (n=1884) investigating infants' antibody response to routine immunizations following Tdap immunization in pregnancy was performed. Geometric mean ratios (GMRs) of antigen-specific immunoglobulin G (IgG) levels were calculated using mixed-effects models. Seroprotection rates were compared using chi-squared tests.

Results

Infants of Tdap-immunized women had significantly lower IgG against pertussis toxin (GMR 0.65; 95%CI 0.57-0.74), filamentous haemagglutinin (FHA) (0.68; 0.53-0.87), pertactin (0.65; 0.58-0.72) and fimbria 2/3 (FIM2/3) (0.41; 0.32-0.52) after primary immunization, compared with infants of unimmunized women. These lower levels persisted after booster immunization for FHA (0.72; 0.61-0.84) and FIM2/3 (0.53; 0.29-0.96). After primary immunization, infants of Tdap-immunized women had lower seroprotection rates against diphtheria (90% [843/973] vs 98% [566/579]; p<0.001) and invasive pneumococcal disease (IPD) caused by 5 Streptococcus pneumoniae (SPN) serotypes (SPN5, SPN6B, SPN9V, SPN19A, SPN23F), and higher seroprotection rates against Haemophilus influenzae type b (short-term and long-term seroprotection rates, 86%[471/547] vs 76%[188/247] and 62%[337/547] vs 49%(121/247), respectively, all p=0.001). After booster immunization, seroprotection rates against diphtheria and tetanus were 99% (286/288) and (618/619) in infants of Tdap-immunized women, respectively.

Conclusions

Infants of Tdap-immunized women in pregnancy had lower IgG levels against pertussis, diphtheria and some SPN serotypes after their immunization compared with infants of unimmunized women. Enhanced surveillance of pertussis, diphtheria and IPD in infants is needed to determine the clinical significance of these findings.

Systematic review registration

CRD42017079171.

SUBMITTER: Abu-Raya B

PROVIDER: S-EPMC8299947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine could prevent infant pertussis.ObjectiveTo evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine.Design, setting, and participantsPhase 1-2, randomized, double-blind, placebo-controlled, clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks' gestation, with crossover immunization postpartum.InterventionsTdap vaccination at 30 to 32 weeks' gestation or postpartum.Main outcomes and measuresPrimary outcomes were maternal and infant adverse events, pertussis illness, and infant growth and development until age 13 months. Secondary outcomes were antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months' postpartum, and in infants at birth, at 2 months, and after the third and fourth doses of DTaP.ResultsNo Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 26 (78.8% [95% CI, 61.1%-91.0%]) and 12 (80% [95% CI, 51.9%-95.7%]) pregnant and postpartum women, respectively (P > .99). Systemic symptoms were reported in 12 (36.4% [ 95% CI, 20.4%-54.9%]) and 11 (73.3% [95% CI, 44.9%-92.2%]) pregnant and postpartum women, respectively (P = .03). Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy vs postpartum (eg, pertussis toxin antibodies: 51.0 EU/mL [95% CI, 37.1-70.1] and 9.1 EU/mL [95% CI, 4.6-17.8], respectively; P < .001) and in their infants at birth (68.8 EU/mL [95% CI, 52.1-90.8] and 14.0 EU/mL [95% CI, 7.3-26.9], respectively; P < .001) and at age 2 months (20.6 EU/mL [95% CI, 14.4-29.6] and 5.3 EU/mL [95% CI, 3.0-9.4], respectively; P < .001). Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP.Conclusions and relevanceThis preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy.Trial registrationclinicaltrials.gov Identifier: NCT00707148.

Project description:Background: Optimal timing of gestational tetanus-diphtheria-acellular pertussis (Tdap) vaccination is not well-defined. No well-established specific anti-pertussis antibody level correlates with protection, suggesting the importance of antibody quality such as avidity. We aimed to determine the effect of timing of vaccination with Tdap in pregnancy on the avidity of cord anti-pertussis toxin (PT) immunoglobulin G (IgG). Methods: Prospective study of newborns in a tertiary hospital (Melbourne, Australia) born to women vaccinated with Tdap in pregnancy. Ammonium thiocyanate was used as a bond-breaking agent to measure the avidity of anti-PT IgG using concentrations between 0.25 M (to measure low avidity antibodies) and 3 M (to measure very high avidity antibodies). Anti-PT IgG levels achieved at each ammonium thiocyanate concentration in cord samples of women vaccinated during 28-32 weeks gestation (WG) vs. 33-36 WG, and women vaccinated 5-12 vs. 1-4 weeks prior to delivery were compared using t-tests. Results: Newborns of women vaccinated with Tdap during 28-32 WG (n = 43) had statistically significant higher concentrations of medium and high avidity anti-PT IgG compared with newborns of women vaccinated during 33-36 WG (n = 47), 11.6 IU/ml (95% CI, 8.8-15.2) IU/ml vs. 6.7 IU/ml (95% CI, 5.2-8.6) and 10.1 IU/ml (95% CI, 7.4-13.8) vs. 5.7 (95% CI, 3.6-8.9) IU/ml (p = 0.007 and p = 0.035), respectively. Newborns of women vaccinated 5-12 weeks before delivery (n = 64) had statistically significant higher concentrations of high and very high avidity anti-PT IgG compared with newborns of women vaccinated within 4 weeks before delivery (n = 25), 10.3 IU/mL (95% CI, 7.9-13.4) vs. 3.3 IU/mL (95% CI, 1.7-6.4), 12.6 IU/mL (95% CI, 9.4-16.9) vs. 4.3 IU/mL (95% CI, 2.2-8.5) (all p < 0.03), respectively. Conclusions: Quantification of levels of anti-PT IgG with different avidities demonstrated that pertussis vaccination 5-12 weeks before delivery was associated with higher anti-PT IgG avidity compared with vaccination within 4 weeks before delivery. Pertussis vaccination during 28-32 WG was associated with higher anti-PT IgG avidity compared with vaccination during 33-36 WG, supporting vaccination at 28-32 over 33-36 WG for optimal protection against pertussis in infancy.

Project description:ImportanceThe United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified.ObjectiveTo assess the duration of immunity and the effectiveness of DTaP vaccines in US children.Design, setting, and participantsA mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017.InterventionsVaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity.Main outcomes and measuresVaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact.ResultsThis study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.Conclusions and relevanceThe results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.