Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women

Abstract

Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined.In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9-139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3-31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours.Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance.

Safety of Maternal Immunization Against Pertussis: A Systematic Review

“…However, moderate-to-severe injection site pain was more frequent in pregnant women than nonpregnant women in one study [34]. Injection site reactions assessed over 7 days were more common after Tdap than placebo in one small clinical study [13] but occurred at similar rates over 48 h in another slightly larger study [40]. Systemic and local reactions occurred at similar frequencies in pregnant women receiving Tdap and those receiving tetanus vaccines in two clinical studies [35,36].…”

“…The most commonly reported reactions were injection site reactions, consistent with the Tdap label. While injection site reactions such as pain/tenderness, induration/swelling, itching, and erythema/redness were reported after Tdap/ Tdap-IPV administration in most clinical studies, pregnancy was not considered to have increased the rates of these events [13,34,[36][37][38]40]. However, moderate-to-severe injection site pain was more frequent in pregnant women than nonpregnant women in one study [34].…”

“…Fifteen studies reported vaccine reactogenicity among pregnant women following immunization with Tdap or Tdap-IPV, among which nine were prospective clinical trials [13,[34][35][36][37][38][39][40][41] and six were database analyses [42][43][44][45][46][47] (Table 1). The most commonly reported reactions were injection site reactions, consistent with the Tdap label.…”

Immune interference (blunting) in the context of maternal immunization with Tdap-containing vaccines: is it a class effect?

“…We defined blunting as reported statistically significant lower GMC levels (based on non-overlapping 95% confidence intervals (CI) or p-values) against antigens included in DTaPcontaining vaccines when comparing immunogenicity in infants born to mothers who were vaccinated with Tdap-containing vaccines during pregnancy to a control group (infants born to mothers not exposed to Tdap during pregnancy) after primary immunization and/or booster dose. Of note, several papers reported significant p-values (p < 0.05) with overlapping 95% CI [19][20][21][22][23][24][25]. We adopted the approach to consider these papers as reporting statistically significant lower GMC levels between the two groups and provided point estimates and 95% CI (Table 2) for readers to make their own assessment whether the reported statistical significance refers to a real difference in GMC levels or haphazard reporting.…”

“…Nine (out of 11) studies reported significantly lower responses to one or more pertussis antigens after completion of the primary vaccination series in infants whose mothers received Tdap during pregnancy compared to infants whose mothers received no vaccine, placebo, or a non-pertussis-containing vaccine during pregnancy ( Table 2). Seven studies reported significantly lower anti-pertussis toxoid (PT) GMC levels [15][16][17][20][21][22]27,28,30], six studies reported significantly lower anti-filamentous hemagglutinin (FHA) GMC levels [15][16][17]20,21,23,27,30] and five studies reported significantly lower anti-pertactin (PRN) GMC levels [20,22,24,27,30] after primary vaccination. One randomized controlled trial (RCT) from Mexico reported lower responses to PT, after maternal immunization with Adacel (Sanofi Pasteur) and primary vaccination with Pentaxim (Sanofi Pasteur) [22].…”