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.     

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.     

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.     

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.     

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.     

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease

BackgroundImmunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity.AimsThis study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine.MethodsWe conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose.ResultsOur study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups.ConclusionsAnti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.     

Infant antibody levels following 10-valent pneumococcal-protein D conjugate and DTaP-Hib vaccinations in the first year of life after maternal Tdap vaccination: An open-label,parallel, randomised controlled trial

BackgroundMaternal antibody levels after Tdap vaccination during pregnancy may affect infant primary antibody responses to pertussis, Tetanus toxoid (TT), Diphtheria toxoid (DT) vaccinations and pneumococcal vaccines with diphtheria toxin mutants like CRM197 as carrier protein.MethodsMothers were recruited in an open label randomised parallel controlled trial in 2014–2016 through midwifes. They received Tdap [Boostrix] at 30–32 weeks of pregnancy (n = 58) or within 48 h after delivery (n = 60). Infants received DTaP-IPV-Hib-HepB [Infanrix Hexa] and 10-valent protein D conjugated pneumococcal conjugate vaccine (PHiD-CV10 [Synflorix]) at age 3, 5 and 11 months. We now report on infant specific IgG levels towards DT, TT, Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP) and PHiD-CV10 before and after primary- and booster vaccination as secondary study endpoints; pertussis antibodies were the primary endpoint of the study. This trial is registered in clinicaltrialsregister.eu (EudraCT 2012–004006-9) and trialregister.nl (NTR number NTR4314).FindingsPost primary vaccinations, antibody levels to DT, but not TT, were significantly lower after Tdap vaccination during pregnancy compared to controls (GMC ratio 0.4, 95% CI 0.3–0.6 and 0.9, 95% CI 0.6–1.2, respectively). Antibodies to serotype 19F were significantly lower in the maternal Tdap group, whereas there were no differences in antibody levels to Hib PRP and the other 9 pneumococcal serotypes. Post booster vaccinations, no significant differences were observed, except for DT.InterpretationMaternal Tdap vaccination results in significant interference with infants responses not only to DT but also to conjugated pneumococcal vaccines containing DT mutants as carrier proteins. These interactions after maternal Tdap vaccination need to be taken into account when designing infants’ national immunization schedules and choice of vaccines.FundingThe Dutch Ministry of Health, Welfare and Sport.     

Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III,randomized study

BackgroundThis study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults.MethodsIn this phase III, randomized, partially-blind study (NCT01767376), healthy 11–25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated.ResultsNon-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles.ConclusionImmune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents.     

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.     

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.     

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.     

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

Persistence of antibodies following a single dose of Tdap vaccine (tetanus, diphtheria, and five-component acellular pertussis vaccine for use in individuals past childhood) was evaluated in a follow-up 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 titers. Humoral immune responses to all antigens were robust 1 month after initial immunization; antibodies exceeded pre-immunization levels 1, 3, and 5 years later. These data will contribute to selecting the optimal interval for booster doses of Tdap.     

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.     

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.     

Physician attitudes and preferences about combined Tdap vaccines for adolescents

BACKGROUND: Combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) boosters for adolescents are a new strategy to prevent pertussis. We examined the current practices of pediatricians and family physicians regarding adolescent tetanus and diphtheria toxoids (Td) vaccine immunizations and providers' potential adherence to new Tdap recommendations for adolescents. METHODS: Using a brief survey instrument sent to a random sample of pediatricians and family physicians in January 2005, we assessed providers' patterns of administration of Td boosters, barriers to Td boosters, and agreement that pertussis vaccination of adolescents is warranted. Results of analyses in February 2005 were presented to the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) to inform its deliberations regarding adolescent Tdap vaccination. RESULTS: The overall response rate was 56% (57% pediatricians, 55% family physicians). Among 297 respondents (154 pediatricians, 143 family physicians) eligible for analysis because they provide care to adolescents, pediatricians (77%) were significantly more likely than family physicians (51%, p < 0.0001) to report that they routinely administer Td at preventive care visits for adolescents aged 11 to 12 years, but otherwise the specialties were similar in their Td practices. Forty-four percent of respondents cited infrequency of adolescent visits as a barrier to Td immunization. Slightly more than half the sample (57%) agreed or strongly agreed that pertussis is serious enough to warrant replacing Td with Tdap for adolescents; pediatricians (70%) were significantly more likely than family physicians (42%, p < 0.0001) to endorse this statement. CONCLUSIONS: This national survey indicates moderate willingness, stronger among pediatricians than among family physicians, to support recommendations for Tdap among adolescents. In February 2006, CDC released recommendations that adolescents aged 11 to 18 (preferred age 11 to 12) receive a single dose of Tdap in place of Td if they have not already received the latter. Near-term efforts regarding Tdap recommendations must address providers' concerns about infrequent routine visits for adolescents and convince more physicians of the importance of pertussis booster immunization during adolescence.     

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.     

Assessing adolescent immunization options for pertussis in Canada: A cost-utility analysis

BackgroundAdolescent tetanus, diphtheria and pertussis (Tdap) immunization helps prevent pertussis infection. Timing of Tdap receipt represents an important facet of successful adolescent pertussis immunization. Potential strategies for timing of vaccine administration are each associated with different benefits – including disease prevention – and costs. The objective of this study was to assess the cost-utility of adolescent pertussis immunization strategies in Canada.MethodsA cost-utility analysis was conducted using a pertussis disease history-simulating Markov model, with adolescents (beginning at age 10 years) as the cohort of interest. The model assessed three Tdap vaccination strategies: (1) immunization of 10 year olds, (2) removal of adolescent vaccination, and (3) immunization of 14 year olds (status quo). The analysis was conducted from a healthcare payer perspective and used a lifetime time horizon. Primary outcomes included life years, quality-adjusted life years (QALYs), health system costs, and an incremental cost-effectiveness ratio (ICER). Costs and outcomes were discounted at 1.5 percent annually. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty.ResultsThe current recommended adolescent immunization strategy (at age 14) resulted in an average of 40.4432 expected QALYs and $26.28 per individual. This strategy was dominated by immunization at 10 years and no immunization. Compared to no immunization, immunizing adolescents at age 10 had an ICER of $74,899 per QALY. Results were most sensitive to the incidence of pertussis and the utility of moderate or severe pertussis. At a cost-effectiveness threshold of $50,000/QALY, removal of adolescent vaccination represented the most cost-effective strategy in 78% of simulations.ConclusionAnalysis assumes a policy context where immunization of pregnant women is recommended. Findings suggest that alternate adolescent Tdap vaccine strategies – either immunization of 10 year olds, or removal of the adolescent vaccine – are more cost-effective than the current practice of immunizing 14 year olds.