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This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-μg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5–3.0]) and anti-tetanus (1.8 [1.1–2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4–54.6]), anti-pertactin (19.2% [4.4–38.1]), and anti-tetanus (30.0% [3.6–52.7]) antibodies. For adolescents, in the 3000-μg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 μg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p). •Tdap-1018 was generally well tolerated in adults and adolescents.•Tdap-1018 3000 μg induced similar or higher immune responses than Boostrix.•The results support continued development of a Tdap booster adjuvanted with CpG 1018.

•To avoid a global pertussis resurgence, booster Tdap immunization is recommended.•Global shortages of acellular pertussis vaccines have been reported.•Safety and immunogenicity of SIIPL Tdap was compared to an approved Tdap vaccine.•SIIPL Tdap immune responses were non-inferior to comparator Tdap vaccine.•SIIPL Tdap was safe and well tolerated. This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46.

Vaccinating women against pertussis in pregnancy protects young infants from severe disease and death. Vaccination-induced maternally derived antibodies, however, might subsequently modulate (and specifically blunt) the infant's serological response to their primary series of pertussis vaccinations. We examined the effect of pertussis immunisation in pregnancy on the immunogenicity of primary acellular or whole-cell pertussis vaccines in a west African cohort. GaPs was a randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. We used a predefined block randomisation scheme to randomly assign healthy, HIV-negative, pregnant participants (1:1) to receive a pertussis-containing (tetanus-diphtheria-acellular pertussis-inactivated polio virus [Tdap-IPV]) or tetanus-toxoid only vaccine at 28–34 weeks' gestation. At the same time, their infants were randomly assigned (1:1) to receive diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole-cell pertussis (DTwP) primary vaccine at 8, 12, and 16 weeks postnatally. Participants and trial staff were masked to the allocation of the maternal vaccine. The field team and participants became unmasked to the allocation of the infant vaccine at 16 weeks; laboratory staff and all other investigators remained masked to infant vaccine allocation until the end of the trial. The primary outcome was geometric mean concentration (GMC) of infant pertussis toxin-specific antibodies at 20 weeks and 9 months postnatally and was assessed in infants who received all three doses of the primary vaccine. Secondary outcomes included memory B-cell responses, and exploratory outcomes were total pertussis-specific antibody binding concentrations and functional antibody titres (pertussis toxin-specific neutralising activity [PTNA] and serum bactericidal activity [SBA]). Vaccine reactogenicity was assessed in mothers and infants for 3 days after each vaccine dose. Pregnant women had an extra safety visit 7 days after vaccination. The study is registered with ClinicalTrials.gov, NCT03606096. Between Feb 13, 2019, and May 17, 2021, we enrolled 343 maternal–infant pairs. 239 (77%) infants were included in the per-protocol immunogenicity analysis. Among infants of mothers receiving Tdap-IPV in pregnancy, at 20 weeks postnatally, the GMCs of anti-pertussis toxin IgG were more than three-fold lower in infants vaccinated with three doses of DTwP (n=64) than in infants vaccinated with three doses of DTaP (n=53; adjusted geometric mean ratio 0·28, 98·75% CI 0·16–0·50). This difference persisted up to 9 months (0·31, 0·17–0·55). Conversely, among infants born to tetanus toxoid-immunised mothers, post-vaccination GMCs of anti-pertussis toxin IgG at 9 months were higher in those vaccinated with DTwP (n=58) than in those vaccinated with DTaP (n=64; 2·02, 1·15–3·55). Tdap-IPV immunisation in pregnancy blunted anti-pertussis toxin IgG following primary vaccination in all infants but particularly in those receiving DTwP, with GMCs of anti-pertussis toxin IgG more than eight-fold lower in DTwP-vaccinated infants born to Tdap-IPV-vaccinated mothers than in DTwP-vaccinated infants born to tetanus toxoid-immunised mothers (0·12, 98·75% CI 0·07–0·22 at 20 weeks; 0·07, 0·03–0·17 at 9 months). Similarly, DTwP-vaccinated infants born to Tdap-IPV-vaccinated mothers also showed significant blunting of PTNA, SBA, total pertussis-specific antibody binding, and memory B-cell responses after primary immunisation, whereas minimal blunting was observed among DTaP-vaccinated infants. However, the absolute levels of these responses generated by DTwP-vaccinated infants remained similar to or, in many cases, were higher than those generated by DTaP-vaccinated infants. There was no difference in reactogenicity between the two maternal vaccines, with most reactions graded 0 or 1. There were no serious adverse events related to vaccination or trial participation. Vaccinating women with Tdap-IPV in pregnancy was safe and well tolerated in a sub-Saharan African setting and boosted the quantity and quality of pertussis-specific antibodies in infants in early life. Although Tdap-IPV was associated with relative blunting of the immune response to the DTwP primary vaccination series, pertussis-specific antibody quality and memory B-cell responses were nevertheless preserved, regardless of the vaccine given during pregnancy. GaPs was conducted as part of the Pertussis Correlates Of Protection Europe (PERISCOPE) consortium, which received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115910. This Joint Undertaking receives support from the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, and the Bill & Melinda Gates Foundation.

In this randomized controlled trial, infants of women immunized with tetanus-diphtheria-acellular pertussis vs tetanus-diphtheria vaccine during pregnancy had higher antibody levels at birth that persisted until 2-4 months of age but lower antibody levels after the primary series at 7 months and booster dose at 12 months. Abstract Background Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration NCT00553228.

•A 3-component Tdap vaccine was administered during the third trimester of pregnancy.•This resulted in high levels of pertussis antibodies in newborns’ cord blood.•The Tdap vaccine had a clinically acceptable safety profile in mothers and their fetuses/newborns.•These data support routine maternal Tdap vaccination to prevent newborn pertussis disease. Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks’ gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. Clinical Trial Registration. ClinicalTrials.gov: NCT02377349.

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. 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 ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants. 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. 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. The Dutch Ministry of Health, Welfare, and Sport.

In developing countries, combined vaccine availability remains limited due to economic constraints, healthcare infrastructure, and supply chain challenges. While some imported combined vaccines are available in China, their accessibility is restricted. Co-administration of individual vaccines presents a viable alternative. This study evaluates the immunogenicity and safety of simultaneous sIPV and DTaP administration to support vaccination policies and improve immunization rates. In this randomized, controlled, open-label, multicenter non-inferiority trial, 702 healthy 3-month-old infants from Shaanxi, Shanxi, and Hebei provinces were enrolled and assigned to three groups: Group 1 (sIPV + DTaP co-administration), Group 2 (sIPV alone), and Group 3 (DTaP alone). Vaccines were administered on a 3-4-5-month schedule. Serum samples were collected pre-vaccination and 30 days post-vaccination to assess antibody responses. Adverse events (AEs) were monitored for safety evaluation. Among 671 infants completing the study (642 per protocol), co-administration (Group 1) demonstrated non-inferior immunogenicity compared to separate administration. Seroconversion rates and geometric mean titers (GMTs) for poliovirus types 1,2 and 3 were comparable between Groups 1 and 2. For anti-PT, FHA, D, T, Group 1 showed non-inferiority to Group 3 in seroconversion. However, anti-PT and anti-FHA geometric mean concentrations (GMCs) were lower (Group 1:anti-PT 31.06 [95% CI: 28.56-33.77], anti-FHA 29.40 [27.68-31.24]; Group 3: anti-PT 39.32 [36.25-42.65], anti-FHA 33.06 [31.01-35.24]). No significant differences were observed in anti-D and anti-T GMCs. AE rates were similar across groups, with local reactions (e.g., induration) more frequent in Group 1 (6.84%) than in Group 2 (0.85%). Systemic AEs (primarily grade 1-2 fever) did not differ significantly. Co-administration of sIPV and DTaP is immunogenically non-inferior to separate administration and demonstrates comparable safety. This strategy is feasible and may support simplified immunization schedules in China. ClinicalTrials.gov, identifier NCT04053010.

Pertussis remains a significant global public health challenge, particularly in China, where no licensed pertussis-containing vaccines are available for individuals aged 6 years and older. This blind, randomised, and controlled phase I clinical trial evaluated the safety and immunogenicity of the Tetanus, Reduced Diphtheria, and Acellular Pertussis (Five Components) Combined Vaccine, Adsorbed (Tdcp). Participants aged 6 years and above were divided into three age subgroups (6–11, 12–17, and ≥18 years) and randomised to receive Tdcp or control vaccines (PPV23 or DT). Safety endpoints included the incidence of adverse reactions within 30 days post-vaccination, while immunogenicity was assessed through seroconversion rates and geometric mean concentrations (GMCs) of anti-DT, TT, PT, FHA, PRN, and FIM 2&3 antibodies at 30 days post-vaccination. Among 178 participants, the incidence of total adverse reactions in the Tdcp group was 54.62%, primarily local reactions such as pain and itching, with no significant differences compared to controls (p > 0.05). Immunogenicity analysis revealed robust immune responses in the Tdcp groups, with seroconversion rates for pertussis-related antigens exceeding 75% in all age groups. The GMCs for anti-PT antibodies reached 125.60 IU/mL, 150.28 IU/mL, and 131.14 IU/mL in the ≥18 years, 12–17 years, and 6–11 years of Tdcp groups, respectively. Overall, the Tdcp vaccine demonstrated a good safety profile and robust immunogenicity in participants aged 6 years and above. The inclusion of five pertussis antigens, particularly PT, elicited strong immune responses, supporting its potential as an effective booster vaccine for adolescents and adults.

Background Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. Methods We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. Results We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. Conclusion Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. Trial registration PROSPERO CRD42018087814 , CRD42018090357 .

Background. We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in Wisconsin during 2012. Methods. We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates [(1 - IRR)*100%], by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression. Results. Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval [CI], 55.2%-86.5%) for receipt during 2012,68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 [95% CI, .52-74]). Conclusions. Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history.