Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine

Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap.     

Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine

The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix^®, GlaxoSmithKline Biologicals; Tdap-B: or Adacel^®, Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).     

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.     

Immunogenicity and reactogenicity of co-administered tetanus-diphtheria-acellular pertussis (Tdap) and tetravalent meningococcal conjugate (MCV4) vaccines compared to their separate administration

In the United States, co-administration of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine and tetravalent meningococcal conjugate vaccine (MCV4) is recommended in adolescents. In this clinical study, 1341 adolescents received Tdap (Boostrix® GlaxoSmithKline) and MCV4 (Menactra®, Sanofi-Pasteur) simultaneously or sequentially one month apart. Co-administration of Tdap + MCV4 was well tolerated and immunogenic, resulting in high levels of antibodies against diphtheria, tetanus, pertussis and meningococcal serogroup A,C,W-135 and Y antigens. The data provide support for current recommendations for co-administration of Tdap and MCV4 vaccines at the same office visit.     

Tolerability and antibody response in adolescents and adults revaccinated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) 4-5 years after a previous dose

Background

Although decennial adult boosters of tetanus and diphtheria toxoids are recommended in Canada and the United States, a second dose of pertussis vaccine is not currently recommended for adults.

Methods

This open-label, postmarketing, multicenter study evaluated the tolerability and immunogenicity of a second dose of an adult formulation of tetanus, diphtheria, and pertussis vaccine (Tdap) in adolescents and adults 5 years after a first dose.

Results

A total of 545 participants from previous Tdap vaccine studies, ranging in age from 15 to 69 years, participated in this study. Of these participants, 94.2% had at least one solicited adverse event after the booster dose such as injection-site erythema (28.6%), swelling (25.6%), or pain (87.6%) or a systemic adverse event such as myalgia (61.0%), headache (53.2%), malaise (38.2%), or fever (6.5%). These adverse events were slightly more frequent than after the initial dose. Postvaccination, 100% of participants had a tetanus antibody level ≥0.10 IU/mL and 95% had a diphtheria antibody level ≥0.10 IU/mL. For pertussis, 82.1% (pertussis toxoid), 96.7% (filamentous hemagglutinin), 95.6% (pertactin), and 99.8% (fimbriae) had a postvaccination antibody threshold of ≥50 EU/mL.

Conclusion

A second dose of Tdap vaccine 5 years after the initial dose was well tolerated and immunogenic in adolescents and adults.     

Immunogenicity and safety of a tetanus toxoid,reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19–64 years of age

Purpose

This study was conducted to assess the immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine containing three pertussis antigens (Boostrix^®, Tdap3v), currently licensed in the US for use in adolescents 10–18 years of age, in adults 19–64 years of age.

Methods

2284 healthy adults, aged 19–64 years, were randomized to receive a single dose of Tdap vaccine, either Tdap3v or a five-pertussis component Tdap vaccine (Adacel^®, Tdap5v) licensed for adult use in the US. Blood samples were taken before and 1 month after vaccination. Reactogenicity was assessed for 15 days after vaccination.

Results

Tdap3v was comparable to Tdap5v in eliciting seroprotective levels of antibodies to diphtheria and tetanus toxoids, with >98% of subjects having post-vaccination seroprotective antibody levels (≥0.1 IU/mL) against diphtheria or tetanus toxoids. The pertussis components of Tdap3v were shown to be immunogenic in adults, with booster responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) observed in 77.2%, 96.9%, and 93.2%, respectively, of Tdap3v recipients, and in 47.1%, 94.0%, and 91.7%, respectively, of Tdap5v recipients. Anti-pertussis antibody GMCs in Tdap3v recipients exceeded those observed in infants following primary DTaP vaccination, in whom efficacy against pertussis disease was subsequently demonstrated. Injection site reactions (pain, redness, and swelling) and fever ≥37.5 °C (99.5 °F) were reported significantly more often (p < 0.05) by Tdap5v recipients than by Tdap3v recipients. Fatigue preventing normal daily activities was reported by a small but significantly greater percentage of Tdap3v recipients (2.5%) than Tdap5v recipients (1.2%, p < 0.05).

Conclusion

In adult recipients, Tdap3v was comparable to an approved Tdap vaccine in providing seroprotection against diphtheria and tetanus, and produced immune responses to pertussis antigens consistent with protection against disease. The overall safety profile of Tdap3v was generally comparable to that of Tdap5v [NCT #106316].     

Immunogenicity of a low-dose diphtheria,tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria,tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap–IPV, Repevax^®; Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis^®; Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap–IPV, Tetravac^®; Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection.All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01 IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap–IPV, Tdap + OPV and DTap–IPV, respectively, had protective antitoxin levels greater than 0.1 IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV.Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.     

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.     

Immune response to a Tdap booster in vertically HIV-infected adolescents

BackgroundPertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce.ObjectiveTo evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL).MethodologyThirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP.ResultsMean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group.ConclusionsBoth groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.     

Pertussis immunization in paediatric healthcare workers: Knowledge,attitudes, beliefs,and behaviour

Healthcare workers’ (HCWs) knowledge, attitudes, and beliefs regarding pertussis immunization were assessed and compared to the rate of vaccine uptake. A questionnaire was distributed to employees at a paediatric and maternity tertiary care centre. Respondents were then offered a dose of the tetanus, diphtheria, and acellular pertussis vaccine (Tdap) at a free vaccine clinic. In total, 529 out of 3051 (17%) employees completed the survey and 61 received the Tdap vaccine. Although 76% of participants were willing to be immunized, only 15% presented to the clinic. There is a widespread acceptance of pertussis immunization among paediatric HCWs. Stated intentions may be poorly predictive of behaviour. Education and institutional or public funding may improve vaccine uptake.     

Immune responses in adults to revaccination with a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine 10 years after a previous dose

Background

Although decennial adult boosters of tetanus and diphtheria toxoids are recommended in Canada and the United States, a second dose of pertussis vaccine during adulthood is not currently recommended.

Methods

This open-label, multicenter study compared the safety and immunogenicity of a first dose of an adult formulation of tetanus, diphtheria, and acelluar pertussis vaccine (Tdap) with a repeat dose of Tdap in adults who had received Tdap 10 years previously.

Results

A total of 769 participants ranging in age from 20 to 72 years took part in this study; 92.3% of naïve and 92.7% of repeat-dose participants had at least one solicited adverse event. Injection-site pain (84.4% and 87.8%), erythema (29.7% and 23.1%), and swelling (23.3% and 20.5%), and myalgia (53.5% and 60.1%), headache (37.6% and 40.6%), malaise (29.0% and 29.4%), and fever (4.9% and 4.2%) were the most common solicited adverse events reported in the naïve and repeat-dose groups, respectively. Postvaccination antibody levels ≥0.1 IU/mL were achieved by 99.7% of the naïve-group participants and all of the repeat-dose participants for tetanus and 96.1% of the naïve group and 98.5% of the repeat-dose group for diphtheria, both meeting the predefined noninferiority criteria. For pertussis antibodies, anti-PT (89.2 EU/mL vs. 116 EU/mL) was higher in the repeat-dose group, anti-FHA (249 vs. 214) and anti-PRN (216 vs. 266) were similar, and anti-FIM (1015 vs. 779) was higher in the naïve group. Noninferiority criteria were met for all antigens except for anti-FIM.

Conclusion

A repeat dose of Tdap vaccine 10 years after the first dose was well tolerated and immunogenic in adults (ClinicalTrials.gov identifier: NCT00712959).     

Tetanus and pertussis vaccination coverage among adults aged ≥ 18 years --- United States, 1999 and 2008

In 2005, the Advisory Committee on Immunization Practices (ACIP) recommended that the newly licensed tetanus, diphtheria, and acellular pertussis (Tdap) vaccine replace a single decennial dose of tetanus diphtheria (Td) vaccine for persons aged 10-64 years. According to these recommendations, Tdap may be used to protect against pertussis even when <10 years have passed since the most recent tetanus vaccination. For adults with infant contact and health-care personnel (HCP) with direct patient contact (two groups at increased risk for transmitting pertussis to those who are most susceptible), the single recommended Tdap dose is suggested to be administered as soon as 2 years after the last tetanus vaccination. To assess changes in tetanus vaccination coverage and the use of Tdap among U.S. adults, CDC analyzed data from the National Health Interview Survey (NHIS) for 1999 and 2008. This report summarizes the results of that analysis, which indicated that self-reported tetanus vaccination coverage (vaccination within the preceding 10 years) was 60.4% in 1999 and 61.6% in 2008. Among adults aged 18-64 years, Tdap coverage was estimated to be 5.9% in 2008. Of those who reported receiving a tetanus vaccination during 2005-2008, 52.0% reported receiving Tdap. Tdap vaccination coverage among adults with infant contact was 5.0% and among HCP was 15.9%. Of those adults with infant contact and HCP who had received a tetanus vaccination during 2005-2008, 60.0% and 60.3% reported receiving Tdap, respectively. Health-care providers should recommend Tdap vaccination to adults aged 18-64 years whose most recent tetanus vaccination was ≥10 years prior; the interval for HCP and persons with infant contact can be as short as 2 years.     

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.     

Pertussis vaccination during pregnancy in Vietnam: Results of a randomized controlled trial Pertussis vaccination during pregnancy

A pertussis vaccination during pregnancy has recently been adopted in several countries to indirectly protect young infants. This study assessed the effect of adding a pertussis component to the tetanus vaccination, in the pregnancy immunization program in Vietnam.A randomized controlled trial was performed. Pregnant women received either a Tdap (tetanus, diphtheria acellular pertussis) vaccine or a tetanus only vaccine between 19 and 35 weeks’ gestational age. Immunoglobulin G (IgG) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous hemaglutinin (FHA) and pertactin (Prn) were measured using commercial ELISA tests, at baseline, 1 month after maternal vaccination, at delivery, and in infants from cord blood and before and after the primary series (EPI: month 2-3-4) of a pertussis containing vaccine.Significantly higher geometric mean concentrations (GMC) were observed for all 3 measured pertussis antigens in the offspring of the Tdap group, up to 2 months of age. One month after completion of the primary infant vaccination schedule, anti-Prn GMC, but not anti-PT and anti-FHA GMCs, was significantly (p = 0.006) higher in the control group.Maternal antibodies induced by vaccination during pregnancy close the susceptibility gap for pertussis in young infants. Limited interference with the infant vaccine responses was observed. Whether this interference effect disappears with the administration of a fourth vaccine dose is further studied.     

A randomized,blinded, placebo-controlled trial comparing antibody responses to homeopathic and conventional vaccines in university students

BackgroundHomeopathic vaccines are licensed in many countries but scientific data to support their use are sparse. The goal of this study was to compare the antibody response of homeopathic and conventional vaccines and placebo in young adults. We hypothesized that there would be no significant difference between homeopathic vaccines and placebo, while there would be a significant increase in antibodies in those received conventional vaccines.MethodsA randomized blinded placebo-controlled trial was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinator, data blood drawers, laboratory technician, and data analyst were blinded.ResultsNone of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo.ConclusionsHomeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.Trial Registry: NCT 02825368.     

Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.     

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus,diphtheria, and 5-component acellular pertussis vaccine in the USA

BackgroundIn a prospective, randomized pivotal phase III clinical trial, the immunogenicity and reactogenicity of a tetanus-diphtheria-acellular pertussis vaccine (Tdap) and a tetanus-diphtheria vaccine (Td) vaccine were studied in participants aged 11–64 years. Here we report antibody persistence through 10 years after vaccination.MethodsParticipants who received Tdap or Td in the original phase III trial and provided pre- and post-vaccination serum samples were recruited to donate sera at 1, 3, 5 and 10 years post-vaccination. Antibody concentrations were measured using standard assay techniques.ResultsInitially, 1457 Tdap and 1152 Td recipients were included; of these, 175 persons from Tdap group were available at the final study bleed point. Nearly all adolescents in both groups had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥95% of vaccinees at 5 and 10 years. Among adults, ≥94% had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥80% at 5 and 10 years. Nearly all participants had tetanus antibodies ≥0.1 IU/mL throughout the study. PT antibodies declined to pre-vaccination levels approximately 5 years post-vaccination; FHA, PRN and FIM antibodies waned at 5 and 10 years but remained several-fold higher than pre-vaccination levels.ConclusionsTdap and Td provide long-lasting protective immune responses against diphtheria and tetanus. Pertussis antibodies following Tdap generally exceeded pre-vaccination levels throughout the study, but showed substantial waning. These data may inform discussion of the need for repeat Tdap booster vaccinations among adults.Trial registrationThe original phase III clinical trial, as well as the 1-, 3-, and 5-year serology follow-up studies were conducted prior to mandatory registration. The 10-year serology follow-up data collection was performed as part of a repeat Tdap administration clinical trial that was registered under clinicaltrials.gov number NCT01439165.     

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults

BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease.MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy.Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised.ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.     

Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec,Canada

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14–15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15–19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009–2012 post-Tdap versus 2000–2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15–19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15–19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013–2017 when an increasing proportion of 15–19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.     

Immunogenicity of reduced antigen content tetanus-diphtheria-acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis-containing vaccine

Three hundred and nineteen adolescents aged 10-12 years who had been previously vaccinated with five doses of acellular pertussis-containing vaccines received single doses of Tdap (reduced-antigen-content tetanus, diphtheria, acellular pertussis) and hepatitis A vaccines in a double-blind crossover trial. Long-term antibody persistence following vaccination with Tdap at pre-school age was similar to that following vaccination with DTaP (diphtheria-tetanus-acellular pertussis). After the sixth dose booster, Tdap induced a vigorous immune response, consistent with protection against diphtheria, tetanus and pertussis diseases.