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.     

Recurrence of extensive injection site reactions following DTPa or dTpa vaccine in children 4-6 years old

Objectives

The aim of this study was to compare the immunogenicity and reactogenicity of a lower dose diphtheria, tetanus and pertussis vaccine (dTpa) with the recommended vaccine (DTPa) given as a fifth dose to 4-6-year old children who previously experienced an extensive injection site reaction (ISR).

Material and methods

Children aged 4-6 years who had experienced an extensive ISR following a 4th dose of DTPa were recruited and randomly assigned to receive either the recommended DTPa or the lower dose dTpa vaccine. Parents recorded local reactions and systemic events for 15 days following vaccination. Immunogenicity was assessed pre and post vaccination by ELISA for diphtheria (D), tetanus (T), pertussis toxin (PT), filamentous haemagglutinin (FHA), and pertactin (PRN).

Results

A total of 53 participants were vaccinated. There was a 72% recurrence rate of ISR, with a trend (p = 0.055) towards fewer ISR in the dTpa (61.5%) compared with the DTPa group (85.2%). There was no difference in reports of pain or irritability between groups. All participants had seroprotective levels of antibody to D and T and seroresponse to each of the 3 pertussis antigens following vaccination with higher GMCs in DTPa vs dTpa group. There was no increase in antibody avidity observed post vaccination, regardless of vaccine given.

Conclusion

Recurrence of ISR with the 5th dose of diphtheria, tetanus and pertussis vaccination in children who have previously experienced an extensive ISR is high. Vaccination with a dTpa vaccine may reduce the risk of fifth dose ISR.     

Barriers to early uptake of tetanus, diphtheria and acellular pertussis vaccine (Tdap) among adults-United States, 2005-2007

Background

The tetanus, diphtheria and acellular pertussis vaccine (Tdap) was recommended by the Advisory Committee on Immunization Practices (ACIP) for U.S. adults in 2005. Our objective was to identify barriers to early uptake of Tdap among adult populations.

Methods

The 2007 National Immunization Survey (NIS)-Adult was a telephone survey sponsored by the Centers for Disease Control and Prevention (CDC). Immunization information was collected for persons aged ≥18 years on all ACIP-recommended vaccines. A weighted analysis accounted for the complex survey design and non-response.

Results

Overall, 3.6% of adults aged 18-64 years reported receipt of a Tdap vaccination. Of unvaccinated respondents, 18.8% had heard of Tdap, of which 9.4% reported that a healthcare provider had recommended it. A low perceived risk of contracting pertussis was the single most common reason for either not vaccinating with Tdap or being unwilling to do so (44.7%). Most unvaccinated respondents (81.8%) indicated a willingness to receive Tdap if it was recommended by a provider.

Conclusions

During the first two years of availability, Tdap uptake was likely inhibited by a low collective awareness of Tdap and a low perceived risk of contracting pertussis among U.S. adults, as well as a paucity of provider-to-patient vaccination recommendations. Significant potential exists for improved coverage, as many adults were receptive to 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.     

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].     

Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005-2010

Background

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was not licensed for use in adults aged ≥65 years due to lack of sufficient efficacy and safety data.

Objective

To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) among adults aged ≥65 years who received Tdap vaccine ‘off-label’ to assess for potential vaccine safety concerns.

Methods

We searched VAERS for US reports of adverse events (AEs) in subjects aged ≥65 years who received Tdap vaccine from 9/1/2005 to 9/08/2010. Medical records were requested for all reports coded as serious (death, hospitalization, prolonged hospitalization, permanent disability, life-threatening-illness). Proportional reporting ratio (PRR) was used to assess for higher proportionate reporting for AEs after Tdap compared with Td reports in subjects aged ≥65 years.

Results

VAERS received 243 reports following Tdap administered to persons aged ≥65 years. Eleven (4.5%) reports were serious, including two deaths. Most common AEs were local reactions in 100 (41.2%) reports. Seventy-eight (32.1%) reports contained coding terms that denoted inappropriate administration of vaccine. ‘Cough’ was the only term associated with disproportionately higher reporting after Tdap compared with Td. Six of seven Tdap reports containing the term ‘Cough’ were non-serious. Clinical review of serious reports identified no unusual patterns of AEs.

Conclusion

Our VAERS review of the ‘off-label’ use of Tdap vaccine in adults ≥65 years did not find any safety concerns that warrant further study. These data will provide useful baseline information to assist CDC and FDA with monitoring efforts as permissive recommendations for Tdap in older persons are adopted.     

An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children

Background

In the US, it is recommended that 4-6 year old children receive diphtheria-tetanus-acellular pertussis (DTaP), inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella (V), and influenza vaccines. Data relating to the concomitant administration of combination DTaP-IPV vaccine (Kinrix™; GlaxoSmithKline Biologicals) and influenza or V vaccines are currently limited. This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix™ when co-administered with MMR (M-M-RII^®, Merck & Co.) and Varivax™ (Merck & Co.) in 4-6 year old children.

Methods

Phase IIIb, open-label, non-inferiority study (NCT00871117). We randomized (1:1) healthy 4-6 year olds to receive Kinrix™ + MMR + V on day 0 (Group 1), or Kinrix™ + MMR on day 0, followed by V at month 1 (Group 2). We measured DTaP-IPV immunogenicity before and 1 month post-vaccination (prior to V vaccination in Group 2). We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events (SAEs) through 6 months post-vaccination.

Results

We enrolled 478 subjects. One month post-vaccination, >95% of subjects in both groups had booster responses to diphtheria, tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers. Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria. Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups, as was reporting of solicited general adverse events within 4 days of vaccination; no vaccine related SAEs were reported.

Conclusion

Concomitant administration of varicella vaccine with Kinrix™ and MMR did not impact the immunogenicity of diphtheria, tetanus, pertussis or poliovirus antigens. Both vaccine regimens were well tolerated. These results support the co-administration of DTaP-IPV, MMR, and V vaccines in 4-6-year-old children, providing protection against multiple diseases in a timely and efficient manner.     

Immunogenicity and safety of one dose of diphtheria,tetanus, acellular pertussis and poliomyelitis vaccine (Repevax) followed by two doses of diphtheria,tetanus and poliomyelitis vaccine (Revaxis) in adults aged ≥40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years

Introduction

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years.

Methods

This open-label, multicentre study was conducted in adults aged ≥40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥0.1 IU/mL by seroneutralization assay [SNA]); tetanus (≥0.1 IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥5 EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥0.01 IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose.

Results

Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5–96.8); tetanus and poliomyelitis, 100% (CI: 98.8–100). Percentage of participants with an antibody titre ≥5 EU/mL against pertussis antigens was ≥95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8–100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%).

Conclusions

This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an adult population to achieve maximal protection against diphtheria, tetanus, poliomyelitis and pertussis simultaneously.     

Tetanus,diphtheria and acellular pertussis (Tdap) vaccination among healthcare personnel—United States, 2011

Background

Health-care personnel (HCP) are at risk for exposure to and possible transmission of vaccine-preventable diseases. Receiving recommended vaccines is an essential prevention practice for HCP to protect themselves and their patients. The tetanus, diphtheria and acellular pertussis vaccine (Tdap) was recommended by the Advisory Committee on Immunization Practices (ACIP) for HCP in 2006 for protection against pertussis. We assessed the recent compliance of U.S. HCP in receiving Tdap vaccination.

Methods

To estimate Tdap vaccination coverage among HCP, we analyzed data from the 2011 National Health Interview Survey (NHIS). Multivariable logistic regression and predictive marginal models were performed to identify factors independently associated with vaccination among HCP.

Results

Overall, Tdap vaccination coverage was 26.9% among HCP aged 18–64 years (95% confidence interval (CI) = 24.3%, 29.7%), which was significantly higher compared with non-HCP among the same age group (11.1%; 10.5–11.8%). Overall, vaccination coverage was significantly higher among physicians (41.5%) compared with nurses (36.5%) and other types of HCP (range 11.7–29.9%). Vaccination coverage was significantly higher among HCP aged 18–49 years compared with those 50–64 years (30.0% vs. 19.2%, respectively). Characteristics independently associated with an increased likelihood of Tdap vaccination among HCP were: younger age, higher education, living in the western United States, being hospitalized within past year, having a place for routine health care in clinic or health center, and receipt of influenza vaccination in the previous year. Marital status of widowed, divorced, or separated was independently associated with a decreased likelihood of Tdap vaccination among HCP.

Conclusions

By 2011, Tdap vaccination coverage was only 26.9% among HCP. Vaccination coverage varied widely by types of HCP and demographic characteristics. Emphasizing the benefits of HCP vaccination for staff and patients, providing vaccinations in the workplace and other non-traditional settings, and providing Tdap at no charge may help increase Tdap vaccination among HCP in all health-care settings.     

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).     

Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix(®)) in adults 55 years of age and over: a sub-analysis of four trials

Background

Older adults, especially those over 65 years, are at risk of more severe morbidity from diphtheria, tetanus and pertussis and may transmit pertussis to unvaccinated or not yet fully vaccinated infants, but data on their response to reduced-antigen-content tetanus, diphtheria and acellular pertussis (dTpa) vaccines are lacking.

Methods

A sub-analysis pooled immunogenicity results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised, controlled clinical trials of dTpa vaccine (Boostrix^®, GlaxoSmithKline Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix^® IPV).

Results

Seroprotective antibody levels were achieved by 82.8% for diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response rate, defined as initially seronegative subjects [<5 EU/mL] reaching ≥5 EU/mL; or a ≥2-fold increase in antibody concentration if initially seropositive was 89.2% for pertussis toxoid, 95.8% for filamentous haemagglutinin and 94.5% for pertactin. Post-booster geometric mean concentrations (GMC) increased for all antigens. Post-booster anti-tetanus and anti-PRN GMCs tended to be higher in 55- to 64-year olds than in those aged 65+.

Conclusion

Larger numbers of subjects over 75 years are needed to better define responses in advanced age, but these data suggest that a single booster dose of dTpa or dTpa-IPV induces good immunological responses in most, and that these vaccines could be readily integrated into existing programmes.     

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.     

A Phase II,randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine,MenACYW-TT,in healthy adolescents in the United States

BackgroundMenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10–17 years old) in the United States of America.MethodsIn this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691).The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers <1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination.ResultsNon-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events.ConclusionsThe MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents.     

Assessment of safety and immunogenicity of two different lots of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine manufactured using small and large scale manufacturing process

Background

Hib vaccine can be easily incorporated in EPI vaccination schedule as the immunization schedule of Hib is similar to that of DTP vaccine. To meet the global demand of Hib vaccine, SIIL scaled up the Hib conjugate manufacturing process. This study was conducted in Indian infants to assess and compare the immunogenicity and safety of DTwP-HB + Hib (Pentavac^®) vaccine of SIIL manufactured at large scale with the ‘same vaccine’ manufactured at a smaller scale.

Methods

720 infants aged 6-8 weeks were randomized (2:1 ratio) to receive 0.5 ml of Pentavac^® vaccine from two different lots one produced at scaled up process and the other at a small scale process. Serum samples obtained before and at one month after the 3rd dose of vaccine from both the groups were tested for IgG antibody response by ELISA and compared to assess non-inferiority.

Results

Neither immunological interference nor increased reactogenicity was observed in either of the vaccine groups. All infants developed protective antibody titres to diphtheria, tetanus and Hib disease. For hepatitis B antigen, one child from each group remained sero-negative. The response to pertussis was 88% in large scale group vis-à-vis 87% in small scale group. Non-inferiority was concluded for all five components of the vaccine. No serious adverse event was reported in the study.

Conclusions

The scale up vaccine achieved comparable response in terms of the safety and immunogenicity to small scale vaccine and therefore can be easily incorporated in the routine childhood vaccination programme.     

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.     

Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010

Despite sustained high coverage for childhood pertussis vaccination, pertussis remains poorly controlled in the United States. A total of 16,858 pertussis cases and 12 infant deaths were reported in 2009. Although 2005 recommendations by the Advisory Committee on Immunization Practices (ACIP) called for vaccination with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) for adolescents and adults to improve immunity against pertussis, Tdap coverage is 56% among adolescents and <6% among adults. In October 2010, ACIP recommended expanded use of Tdap. This report provides the updated recommendations, summarizes the safety and effectiveness data considered by ACIP, and provides guidance for implementing the recommendations.     

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.     

Impact and cost-effectiveness of a second tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccine dose to prevent pertussis in the United States

IntroductionThe United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap.MethodsA static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated.ResultsUsing baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years).ConclusionA second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis.     

Immunogenicity and safety of a booster dose of diphtheria,tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV; Repevax) administered concomitantly versus non-concomitantly with an influenza vaccine (Vaxigrip) to adults aged ≥60 years: An open-label,randomised trial

Background

Annual influenza vaccination provides an opportunity to administer a booster dose of diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV) to the elderly. This study evaluated immune responses to and safety of the two vaccines administered concomitantly or sequentially to elderly individuals in France and Germany.

Methods

Individuals aged ≥60 years who had received a diphtheria/tetanus booster within 5–15 years were randomised (1:1) to receive either Tdap-IPV and an inactivated influenza vaccine concomitantly (Group 1) or inactivated influenza vaccine then Tdap-IPV 28–35 days later (Group 2). Antibody titres were measured before and 28–35 days after each vaccination.

Results

The mean age of randomised individuals (n = 954) was 68.8 years. Post-vaccination seroprotection rates (≥0.1 IU/mL for diphtheria/tetanus and ≥8 1/dilution for polio) for Group 1 were non-inferior to Group 2 for diphtheria (85.4% vs. 87.5%), tetanus (both 100%), polio type 1 (99.8% vs. 100%), polio type 2 (both 100%) and polio type 3 (99.3% vs. 99.8%). Similarly, percentages of individuals with pertussis antibodies ≥5 EU/mL for Group 1 were non-inferior to Group 2: pertussis toxin (94.3% vs. 98.1%), filamentous haemagglutinin (99.8% vs. 100%), pertactin (97.3% vs. 96.0%), fimbriae 2 and 3 (91.7% vs. 89.5%). Post-vaccination geometric mean titres of anti-influenza haemagglutinin antibodies for Group 1 were non-inferior to Group 2. Adverse events following administration of Tdap-IPV were similar in both study groups, with no vaccine-related serious adverse events.

Conclusion

Tdap-IPV and inactivated influenza vaccine can be administered concomitantly in the elderly without impairing tolerability or the immune response to either vaccine.     

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.