Immunogenicity of the pentavalent DTwP-HB-Hib vaccine (Shan-5) used in the Thai Expanded Program on Immunization compared to the hexavalent DTaP-HB-Hib-IPV and DTwP-HB-Hib (Quinvaxem) vaccines administered to infants at 2, 4, 6 months of age

BackgroundThe pentavalent DTwP-HB-Hib (Shan-5) vaccine was first introduced into the Thailand Expanded Program on Immunization (EPI) in 2019. The Shan-5 vaccine is administered to infants at 2, 4, and 6 months of age, after initial vaccination with monovalent hepatitis B (HepB) and Bacillus Calmette-Guérin (BCG) vaccines at birth. This study compared the immunogenicity of the HepB, diphtheria, tetanus, and Bordetella pertussis antigens incorporated in the EPI Shan-5 vaccine versus the optional pentavalent (DTwP-HB-Hib) Quinvaxem and hexavalent (DTaP-HB-Hib-IPV) Infanrix-hexa vaccine.MethodsThree-dose Shan-5-vaccinated children were prospectively enrolled at the Regional Health Promotion Centre 5, Ratchaburi province, Thailand, between May 2020 and May 2021. Blood sampling was performed at months 7 and 18. The levels of HepB surface antibody (anti-HBs), anti-diphtheria toxoid (DT) IgG, anti-tetanus toxoid (TT) IgG, and anti-pertussis toxin (PT) IgG were evaluated using commercially available enzyme-linked immunoassays.ResultsAnti-HBs levels of ≥10 mIU/mL were achieved in 100 %, 99.2 %, and 99.2 % of infants in the Shan-5 EPI group, hexavalent group and Quinvaxem group one month after four dose immunization (at 0, 2, 4, 6 months of age), respectively. The geometric mean concentrations of the EPI Shan-5 and hexavalent groups were comparable but were higher than those of the Quinvaxem group. At one month after primary vaccination (month 7), infants in the Shan-5 EPI group had significantly higher levels of anti-DT IgG, anti-TT IgG, and anti-PT IgG than infants in the hexavalent and Quinvaxem groups.ConclusionsThe immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization.     

Immunogenicity of a liquid hexavalent DTaP-IPV-HB-PRP∼T vaccine after primary and booster vaccination of term and preterm infants born to women vaccinated with Tdap during pregnancy

BackgroundVaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) antigens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b (PRP ～ T) vaccine in term and preterm populations.MethodsA prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [Boostrix?, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP ～ T (Hexyon?, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33).ResultsBefore primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs ≥ 10 mIU/mL and anti-PRP ≥ 0.15 µg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]).ConclusionsThese data support the use of DTaP-IPV-HB-PRP ～ T vaccine for primary and booster vaccination in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women.     

Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix(®)): results of two randomized trials

Background

Pertussis can cause significant morbidity in elderly patients, who can also transmit this disease to infants and young children. There is little data available on the use of acellular pertussis vaccines in recipients ≥65 years of age.

Methods

Two studies examined the safety and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine (Boostrix^®) in healthy ≥65 year olds. In Study A subjects received single doses of Tdap and seasonal influenza vaccine either co-administered or given one month apart. In Study B subjects received either Tdap or tetanus-diphtheria (Td) vaccine. Antibodies were measured before and one month after vaccination. Reactogenicity and safety were actively assessed using diary cards.

Results

A total of 1104 subjects 65 years of age and older received a Tdap vaccination in the two studies. In study A, no differences in immune responses to Tdap or influenza vaccine were observed between co-administered or sequentially administered vaccines. In study B, Tdap was non-inferior to Td with respect to diphtheria and tetanus seroprotection, and anti-pertussis GMCs were non-inferior to those observed in infants following a 3-dose diphtheria, tetanus and acellular pertussis (DTaP) primary vaccination series, in whom efficacy against pertussis was demonstrated. Reports of adverse events were similar between Tdap and Td groups.

Conclusions

Tdap was found to be immunogenic in subjects ≥65 years, with a safety profile comparable to US-licensed Td vaccine. Tdap and influenza vaccine may be co-administered without compromise of either the reactogenicity or immunogenicity profiles of the two vaccines.     

FDA approval of expanded age indication for a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine

On July 8, 2011, the Food and Drug Administration (FDA) approved an expanded age indication for the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Originally, Boostrix was licensed in 2005 for persons aged 10 through 18 years, but in 2008, FDA approved an expanded age indication for Boostrix to include persons aged 19 through 64 years. FDA has now expanded the age indication to include persons aged 65 years and older. Boostrix is now licensed for use in persons aged 10 years and older as a single-dose booster vaccination. This notice summarizes the indications for use of Boostrix. Recommendations of the Advisory Committee on Immunization Practices (ACIP) for Tdap vaccines have been published previously. Publication of revised Tdap recommendations within the next year is anticipated.     

Safety review of tetanus toxoid,reduced diphtheria toxoid,acellular pertussis vaccines (Tdap) in adults aged ≥65 years,Vaccine Adverse Event reporting System (VAERS), United States,September 2010–December 2018

IntroductionThe Advisory Committee on Immunization Practices (ACIP) recommends vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in persons ≥65 years of age. To date, few studies have assessed the safety of Tdap in this population. We aimed to summarize reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following receipt of Tdap in this age group.MethodsWe searched for and analyzed U.S. VAERS reports of Tdap among individuals ≥65 years of age submitted from September 1, 2010 through December 31, 2018. We classified reports according to concurrent vaccination, seriousness, and outcome (death, non-death) and determined the frequency of reported adverse events (AEs). For serious reports, we reviewed available medical records. Data mining analyses were undertaken to detect disproportionality in reporting.ResultsVAERS received a total of 1,798 reports following Tdap, of which 104 (6%) were serious. The most common AEs were injection site erythema (26%; n = 468), injection site pain (19%; n = 335), injection site swelling (18%; n = 329), and erythema (18%; n = 321). We identified seven deaths; none were attributed to Tdap. Among serious non-death reports, nervous system disorders (35.1%; n = 34) and infections and infestations (n = 18.6%; n = 18) were most commonly reported. Data mining did not identify any vaccine-AE combination reported more frequently than expected.ConclusionsWe did not identify any new safety concern over nearly a decade of recommended Tdap use among adults ≥65 years of age. Findings from this post-marketing review are consistent with prior post-marketing observations and pre-licensure studies.     

An observational,cohort, multi-centre,open label phase IV extension study comparing preschool DTAP-IPV booster vaccine responses in children whose mothers were randomised to one of two pertussis-containing vaccines or received no pertussis-containing vaccine in pregnancy in England

An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study.Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP₃-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP₅-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP₅-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared.Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP₃-IPV and dTaP₅-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP₃-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22–0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups.The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose.ClinicalTrials.gov registration number: NCT03578120     

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination

IntroductionDuration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations.MethodsBlood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays.ResultsAt 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children.ConclusionsThe pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis.ISRCTN65428640; ISRCTN64117538; NTR4089.     

Interchangeability of Quinvaxem during primary vaccination schedules: Results from a phase IV,single-blind,randomized, controlled,single-center,non-inferiority study

Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP–HepB–Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6–10–14 week schedule) of Tritanrix HB + Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB + Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB + Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB + Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720).     

Tetanus,diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36 weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2 months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2 months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2 months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36 weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36 weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36 weeks of pregnancy was consistently protective against infant ARI in the first 2 months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.     

Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Notes from the field : use of tetanus, diphtheria, and pertussis vaccine (Tdap) in an Emergency Department - Arizona, 2009-2010

Because of an increasing incidence of reported pertussis cases attributed to waning immunity among adults and adolescents, the Advisory Committee on Immunization Practices (ACIP) in 2005 recommended administration of a new, combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) for adolescents and adults aged 11-64 years. ACIP recommended that they receive a single dose of Tdap to replace tetanus and diphtheria toxoid vaccine (Td) for booster immunization against tetanus and diphtheria if they had not previously received Tdap. Adults aged ≥65 years were to receive Td according to ACIP recommendations. To learn whether these age-specific recommendations were being followed in an emergency department (ED), the charts of a sample of patients receiving tetanus vaccines at a large ED were reviewed.     

Comparison of hepatitis B surface antibody levels induced by the pentavalent DTwP-HB-Hib versus the hexavalent DTaP-HB-Hib-IPV vaccine,administered to infants at 2, 4, 6, and 18 months of age,following monovalent hepatitis B vaccination at birth

BackgroundIn Thailand, the hepatitis B (HB) vaccine is administered as a tetravalent vaccine (DTwP-HB) to all infants at 2, 4, and 6 months of age, following an initial vaccination with a monovalent HB vaccine at birth. As part of ongoing vaccine evaluation, we aimed to compare the hepatitis B immunogenicity profiles of children who had received either the pentavalent (DTwP-HB-Hib) or the hexavalent (DTaP-HB-Hib-IPV) vaccine.MethodsTwo groups of infants, whose mothers previously received the tetanus-diphtheria-acellular pertussis vaccine (Tdap), were randomly vaccinated with either pentavalent or hexavalent vaccine at 2, 4, 6, and 18 months of age, following monovalent HB vaccine at birth. Blood samples were obtained at birth, one-month post-primary series immunization (mo 7), pre-booster (mo 18), one-month post-booster (mo 19), and six months post-booster (mo 24). The third group of infants, whose mothers did not receive Tdap, was vaccinated with DTwP-HB-Hib (EPI pentavalent group). Levels of HBsAg, anti-HBc, and anti-HBs were evaluated by means of an automated Chemiluminescent Microparticle Immunoassay.ResultsAnti-HBs levels of ≥10 mIU/ml were achieved in 99.2% (hexavalent group), 99.2% (pentavalent group), and 98.5% (EPI pentavalent group) of infants, after four-dose immunization (at 0, 2, 4, 6 months of age). One month after the additional dose given at 18 months of age, anti-HBs levels of ≥10 mIU/ml were observed in 100% (hexavalent group), 99.2% (pentavalent group), and 93.8% (EPI pentavalent group) of infants. At 24 months of age, higher percentages of infants achieving anti-HBs levels ≥10 mIU/ml were found in the hexavalent group (98.3%) compared to the pentavalent group (86.5%).ConclusionsBoth vaccines were effective in inducing anti-HBs levels of ≥10 mIU/ml, and therefore either can be used as a single formula booster at 18 months of age to simplify vaccine administration under the Expanded Program on Immunization in Thailand.     

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before,with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015.We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3–4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3–4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3–4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18–64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination.Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported.In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3–4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response.The trial is Trials Registry (ANZCTR): ACTRN12613000536763.     

Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women

IntroductionPregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.Materials and methodsPregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).ResultsThere was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.ConclusionsThe reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.     

A quality improvement initiative to increase Tdap (tetanus,diphtheria, acellular pertussis) vaccination coverage among direct health care providers at a children’s hospital

ObjectivesHealth care providers (HCP) are at high risk of acquiring and transmitting pertussis to susceptible family members, co-workers, and patients. Public health authorities recommend administering a single dose of Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine to all adults, including HCP, to increase adult immunity to pertussis. We set a quality improvement goal to increase Tdap vaccination coverage among HCP who provided direct patient care at a children’s hospital from 58% to 90% over 18 months.DesignA multidisciplinary working group comprised of Occupational Health Program (OHP) staff and representatives of various medical services drew from a variety of qualitative methods and previous studies of vaccination programs in the healthcare system to understand barriers to Tdap vaccination within the institution and to develop interventions to increase vaccination rates.InterventionsInterventions included changes to OHP processes, a general education campaign, improved access to vaccine, and personal engagement of HCP by task force members.ResultsOverall vaccination rates increased to 90% over 15 months, a rate that has been sustained by systematically assessing new employees’ vaccination status and vaccinating those without documentation of previous Tdap vaccination.ConclusionsTdap vaccination coverage in our institution was significantly increased by an intensive, multipronged educational campaign, and by improving processes of screening and vaccination of HCP. The use of direct engagement of vaccine hesitant populations to increase vaccination rates warrants further study.     

Cellular and humoral responses to tetanus vaccination in Gabonese children

Protection to tetanus is often not optimal in developing countries due to incomplete vaccination schemes, or decreased efficacy of vaccination. In this study we investigated the immunological response to tetanus booster vaccination in school children living in a semi-urban or in a rural area of Gabon. Tetanus-specific total IgG as well as antibody subclasses of the IgG1, IgG2, IgG3 and IgG4 isotype and the avidity of the dominating IgG1 subclass were determined both before and 1 month after the booster vaccination. In addition, tetanus-specific cytokine responses were determined. We found a polarization towards a T helper 1 (Th1) profile in the semi-urban children, whereas the cytokine responses of the rural children showed a T helper 2 (Th2) skewed response. Furthermore, tetanus-specific antibodies of the different IgG subclasses were all increased upon a tetanus booster vaccination and levels of IgG1 and IgG3 were higher in the rural children. In conclusion, a tetanus booster vaccination induced a stronger Th2 over Th1 cytokine profile to tetanus toxoid (TT) in rural children who showed the highest levels of IgG1 and IgG3 anti-TT antibody responses.     

Adolescent Tdap Vaccine Use Among Primary Care Physicians

PurposeIn 2006 the Advisory Committee on Immunization Practices (ACIP) recommended replacement of the adolescent tetanus and diphtheria toxoids (Td) booster with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). We examined the degree to which pediatricians and family practitioners have adopted this recommendation.MethodsNational mail-based survey of a random sample of 725 pediatricians and 725 family practitioners from January through March, 2007.ResultsOverall response rate was 60%. The majority of respondents indicated they routinely recommended Tdap to adolescents at the preferred age for vaccination, 11–12 years old (87%), and also for “catch up” vaccination among adolescents 13–18 years old (89%). In bivariate analyses, pediatrician specialty, specialty society membership, stocking Tdap in the office, and prior experience diagnosing adolescent pertussis were associated with routinely recommending Tdap to adolescents. In multivariable models adjusting for these factors simultaneously, only pediatrician specialty (OR = 4.8, 95% CI = 2.5–9.3) and stocking Tdap in the office (OR = 14.5, 95% CI = 7.5–28.5) remained significantly associated with routine recommendation. Pediatricians were significantly more likely than family practitioners to accept shorter time intervals for administering Tdap following Td vaccination, and to co-administer Tdap with MCV4. Lack of adolescent visits was the most commonly cited major barrier to adolescent Tdap administration.ConclusionsBased on self report, our results indicate the majority of physicians have adopted recent recommendations from the ACIP to administer Tdap to adolescents. However, specialty-based disparities in attitudes and practices persist, suggesting that ongoing efforts are needed to motivate physicians to recommend this vaccine to adolescents and to clarify how to integrate Tdap with other adolescent vaccinations.     

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria,tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women

BackgroundMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.ObjectivesThe primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).MethodsThis randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.ResultsThe seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).ConclusionMost pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.     

An observational study of antibody responses to a primary or subsequent pertussis booster vaccination in Australian healthcare workers

Adult pertussis vaccination is increasingly recommended to control pertussis in the community. However, there is little data on the duration and kinetics of immunity to pertussis boosters in adults. We compared IgG responses to vaccination with a tetanus, low-dose diphtheria, low-dose acellular pertussis (Tdap) booster at 1 week, 1 month and 1 year post-vaccination in whole-cell (wP)-primed Australian paediatric healthcare workers who had received an adult Tdap booster 5–12 years previously, to those who received their first Tdap booster.Tdap vaccination was well tolerated in both groups. Previously boosted adults had significantly higher pre-vaccination IgG concentrations for all vaccine-antigens, and more were seropositive for pertussis toxin (PT)-specific IgG (≥ 5 IU/mL) (69.5%; 95% confidence interval (CI) 59.5–79.5) than adults in the naïve group (45.2%; 95% CI 32.8-57.5). Tdap vaccination significantly increased IgG responses 1 month post-vaccination in both groups. This increase was more rapid in previously boosted than in naïve adults, with geometric mean fold-increases in PT-IgG at 1 week post vaccination of 3.6 (95% CI 2.9–4.3) and 2.6 (95% CI 2.2–3.2), respectively. Antibody waning between 1 month and 1 year post-vaccination was similar between groups for IgG specific to PT and filamentous haemagglutinin (FHA), but was faster for IgG against pertactin (PRN) in the naïve group (GMC ratio 0.36; 95% CI 0.31–0.42) than the previously boosted group (GMC ratio 0.45; 95% CI 0.39–0.50). At baseline, all but one adult had protective IgG titres against tetanus toxin (TT) (≥ 0.1 IU/mL), and 75.6% in the previously boosted and 61.3% in the naïve group had protective IgG titres against diphtheria toxoid (DT) of ≥ 0.1 IU/mL.This study shows that pertussis immune memory is maintained up to 12 years after Tdap vaccination in wP-primed Australian adults. There was no evidence that pertussis immune responses waned faster after a booster dose. These findings support current recommendations of repeating Tdap booster vaccination in paediatric healthcare workers at least every 10 years. Clinical trials registry: ACTRN12615001262594.