Immunogenicity and Safety of a Newly Developed Tetanus-Diphtheria Toxoid (Td) in Healthy Korean Adolescents: a Multi-center, Randomized, Double-blind, Active-Controlled Phase 3 Trial.

BACKGROUND: Although the combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is recommended at adolescence in developed countries, the tetanus and diphtheria toxoid vaccine (Td), which is less costly, is recommended instead in some parts of the world. A new Td, BR-TD-1001, was developed by a Korean manufacturer for distribution to endemic regions and for use in the initial step of novel Tdap development. METHODS: This phase 3, randomized, double-blind, multi-center trial, conducted in Korea, aimed to evaluate the immunogenicity and safety of BR-TD-1001. Healthy children aged 10 to 12 years were randomized 1:1 to receive either BR-TD-1001 or the control Td (Td-pur, GlaxoSmithKline). Antibodies were measured using enzyme-linked immunosorbent assay. RESULTS: A total of 218 subjects (BR-TD-1001, n = 108; control, n = 110) were enrolled and included in the safety analysis. Vaccine-mediated antibody responses were similar in both groups. We confirmed the non-inferiority of BR-TD-1001 against the control, Td; 100% of both groups achieved seroprotection against diphtheria and tetanus. Furthermore, there was no significant difference between groups in the proportion of participants who demonstrated boost responses against diphtheria and tetanus toxoids. The incidence of solicited local and systemic adverse events (AEs), unsolicited AEs, and serious AEs did not differ significantly between groups. CONCLUSION: The BR-TD-1001 satisfied the immunological non-inferiority criterion against diphtheria and tetanus, with a clinically acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04618939.

Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination.

The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27+ B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG+ and IgA+ memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM+IgD+CD27+ B cells and IgM-only CD27+ B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG+ MBC and IgM+IgD+CD27+ B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG+ MBC, but remained unchanged in IgM+IgD+CD27+ B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1+ICOS+) circulating follicular helper T cells (cTFH), particularly of the CXCR3-CCR6- cTFH2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG+ MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cTFH cells, and are important parameters for consideration in assessing vaccine-induced immune responses.

Vaccination Against Diphtheria and Tetanus as a Way to Activate Adaptive Immunity in Children with Solid Tumors.

Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic.

Effectiveness of booster dose of tetanus and diphtheria toxoids (Td) vaccine in management of recurrent aphthous stomatitis: a prospective, randomized, triple-blind and placebo-controlled clinical trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common oral disease. The activation of the immune system by vaccines might reduce the interactions between oral mucosa and microorganisms. AIM: To evaluate the effect of the tetanus-diphtheria toxoids (Td) vaccine in management of RAS. DESIGN AND SETTING: This prospective, randomized, triple-blind and placebo-controlled clinical trial study was conducted on 70 eligible patients with minor RAS at the dermatology outpatient clinic. METHOD: Finally, a total of 66 participants (48 male, 18 female; mean age: 38.56 ± 10.98 years) completed the study in two groups, one in which colchicine and a single dose of vitamin B6 (placebo group) was treated and one in which colchicine and a single dose of Td vaccine (intervention group) was treated. RESULTS: After six months of follow-up, the patients were evaluated, which revealed significant effects of the Td vaccine on pain intensity, ulcer size, recovery time, and the interval between episodes. At the end of the six month follow-up, 27 patients (81.8%) in the intervention group and 13 patients (39.4%) in the placebo group showed partial or complete recovery, and there was statistically significant difference between the groups (p < .001). Recovery was not significantly associated with sex, education level, marital status and duration of RAS. However, occupation and positive family history of RAS had significant relations with recovery. CONCLUSIONS: A booster dose of Td vaccine had relatively favorable effects on pain intensity and recurrence of RAS, but further research is needed to confirm its efficacy.

Tetanus vaccine-induced human neutralizing antibodies provide full protection against neurotoxin challenge in mice.

Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs-T3, T7, and T9-6-completely protected mice from challenge with 2× LD50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.

Seroprotection rate in adults after 1-dose, 2-dose, and 3-dose series of a reduced-diphtheria-tetanus toxoid vaccine (Td) during a diphtheria outbreak in Thailand.

To evaluate seroprotection of different dosing strategies of reduced-diphtheria-tetanus-toxoid vaccine (Td) for adults during a diphtheria outbreak in Thailand, we enrolled 160 healthcare workers and 161 adults aged 20-60 years old and measured diphtheria antitoxin (DAT) level before administration of a Td vaccine. We scheduled a second Td at 4-8 weeks and a third Td at 6-12 months interval. DAT was measured 4 weeks after each dose. DAT levels of ≥0.1 and ≥1 IU/mL were considered as seroprotective and long-term seroprotective. Persons achieving long-term seroprotection were not given a further dose. The baseline seroprotection rate was 32.6%, which increased to 87.1% (95% confidence interval, 83.4-90.8%) after one dose. The seroprotection rate increased slightly with additional doses. The immune response was lowest among persons 30-49 years of age. We suggest 1-dose Td for adults during a diphtheria outbreak, and a 2-dose series being considered for those born before 1980.

Use of tetanus-diphtheria (Td) vaccine in children 4-7 years of age: World Health Organization consultation of experts.

For lifetime protection against diphtheria and tetanus, the World Health Organization (WHO) recommends six doses of diphtheria and tetanus containing vaccines. Td (reduced diphtheria toxoid, ≥2-5 IU) vaccines are currently licensed for ages 7 years and older, but use of Td vaccine for ages 4 years and older would have advantages for immunization programs in many low- and middle-income countries. For this reason, WHO convened an expert consultation to review the currently available evidence for the use of Td vaccine from 4 to 7 years of age which concluded: (1) no relevant biological difference in immune response in the relevant age group compared with children over 7 years of age; (2) adequate seroprotection in several studies with Td vaccine in the 4-7 age group and many studies using combination vaccines; (3) durable and protective response of at least 9-11 years duration in several longitudinal and modelling studies, (4) less reactogenicity compared with use of full-dose diphtheria vaccine, potentially improving the vaccination experience; and (5) adequate control of diphtheria in several countries using Td-containing combination vaccines in 4-7 year old children. On this basis, the experts concluded that from a programmatic perspective, Td vaccine given in ages 4-7 years, as a second booster dose in a six-dose series, would provide adequate protection against diphtheria and tetanus and recommended steps to include this change in age extension listed in the package insert.

Insurance Reimbursements for Routinely Recommended Adult Vaccines in the Private Sector.

INTRODUCTION: Financial concerns are frequently cited by providers as a barrier to adult vaccination. This study assessed insurance reimbursements to providers for administering vaccines to adults in the private sector. METHODS: This study, conducted in 2018, used the 2016 MarketScan Commercial Claims and Encounters Database and included vaccination visits made by adults aged 19-64 years. Four routinely recommended vaccines targeted at adults were included: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); tetanus and diphtheria toxoids (Td); zoster; and influenza. The mean reimbursements for vaccine purchase and administration were reported and examined by state, metropolitan statistical area, provider type, and insurance plan type. Using the private vaccine purchase price published by the Centers for Disease Control and Prevention (CDC), the study reported the proportion of vaccination visits receiving reimbursements above the CDC-published price. RESULTS: The mean vaccine administration reimbursement was $25.80 for the first dose and $14.71 for additional doses in the same visit. The mean vaccine purchase reimbursement was $44.15 for Tdap, $25.78 for Td, and $216.05 for the zoster vaccine; the unweighted mean for the four examined influenza vaccines was $17.25. Reimbursements varied widely by state. Vaccine reimbursements exceeded the CDC-published price for most visits where Tdap (71.4%), zoster (87.8%), and three of four influenza (61.5%-88.5%) vaccines were administered but only for 25.8% of visits where Td was given. CONCLUSIONS: On average, reimbursements for administering vaccines to privately insured adults were adequate for most private practices. However, providers' financial concerns may vary across geographic locations.

A pathway to developing and testing quality measures aimed at improving adult vaccination rates in the United States.

Despite recommendations for vaccinating adults and widespread availability of immunization services (e.g., pharmacy venues, workplace wellness clinics), vaccination rates in the United States remain low. The U.S. National Adult Immunization Plan identified the development of quality measures as a priority and key strategy to address low adult vaccination coverage rates. The use of quality measures can provide incentives for increased utilization of preventive services. To address the lack of adult immunization measures, the National Adult and Influenza Immunization Summit, a coalition of adult immunization partners led by the Immunization Action Coalition, Centers for Disease Control and Prevention, and National Vaccine Program Office, spearheaded efforts to (1) identify gaps and priorities in adult immunization quality performance measurement; (2) explore feasibility of data collection on adult immunizations through pilot testing and engaging stakeholders; and (3) develop and test quality measure specifications. This paper outlines the process by which a public-private partnership drove the development of two adult immunization performance measures-an adult immunization status measure for influenza, tetanus and diphtheria (Td) and/or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), herpes zoster and pneumococcal vaccines, and a prenatal immunization status measure for influenza and Tdap vaccinations in pregnant women. These measures have recently been added to the 2019 Healthcare Effectiveness Data and Information Set (HEDIS®), a widely used set of performance measures reportable by private health plans.

Observational studies of non-specific effects of Diphtheria-Tetanus-Pertussis vaccines in low-income countries: Assessing the potential impact of study characteristics, bias and confounding through meta-regression.

INTRODUCTION: It has been suggested that some vaccines have effects beyond protection against the diseases they target, called non-specific effects (NSEs). In 2016, a systematic review by Higgins et al., commissioned by the WHO Strategic Advisory Group of Experts (SAGE) on immunization, estimated the relative risk (RR) of all-cause mortality after whole-cell Diphtheria-Tetanus-Pertussis (DTwP) vaccination to be 1.38 (95% CI: 0.92-2.08), and described these potential NSEs as inconsistent. However, the selection of studies for meta-analysis, based on their proneness to bias and confounding, was debated. OBJECTIVE: To identify study characteristics and postulated risks of bias and confounding that might have impacted the RR of all-cause mortality after DTwP vaccination in observational studies conducted in low-income countries. METHODS: Based on methodological considerations on study design and analysis, we systematically assessed all 17 DTwP studies from the Higgins et al. review for risk of selection bias, exposure and outcome misclassification, confounding and differential co-interventions. We used meta-regression to assess the impact of study characteristics and the postulated risks of bias and confounding on the RR estimates, and looked for outlying and influential risk estimates. Permutation tests were performed to control for false-positive findings. RESULTS: The overall RR of all-cause mortality after DTwP vaccination including all but one outlying and influential study was 1.32 (95% CI: 0.83-2.08). Based on uni-variable meta-regression, we found that study location (p = 0.01), studies using the landmark approach (p = 0.015) and studies at high risk of exposure misclassification (p = 0.036) were significantly associated with increased RR estimates whereas studies at high risk of selection bias (p = 0.059) showed borderline significance. The results further suggest these effect modifiers are clustered in studies conducted in West-Africa. CONCLUSION: The increased RR of all-cause mortality after DTwP might be confined to West-African countries and/or certain postulated risks of bias might have inflated these RRs.

Immunogenicity and safety of a tetanus-diphtheria vaccine and a 13-valent pneumococcal conjugate vaccine after concomitant vaccination in ≥ 50-year-old adults.

BACKGROUND: When two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction. METHODS: Subjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively. RESULTS: A total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p <  0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred. CONCLUSIONS: Concomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles. TRIALS REGISTRATION: NCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

The Effect of Concurrent Tetanus-diphtheria Vaccination on the Antibody Response to Rabies Vaccine: A Preliminary Study.

The number of studies in the literature investigating the effect of tetanus vaccination on rabies prophylaxis is rather limited. In this study, we aimed to investigate the effect of concurrent tetanus-diphtheria (Td) vaccination on the antibody response to rabies vaccine. The data of consecutive 80 patients who presented to Sakarya University Training and Research Hospital, Department of Emergency due to rabies suspected exposure between 15 October 2012 and 12 June 2013 were enrolled to this study. Postexposure rabies prophylaxis had been given to all cases, however concurrent tetanus vaccination had been administered to some of them according to their need. Cases were divided into two parts according to their receipt of tetanus prophylaxis as rabies only group (group R, n=37), and rabies and tetanus-diphtheria group (group R+Td, n=43). Rabies antibody levels were tested in sera of the cases at first and postvaccination 21st day. The median antibody levels of each group were measured and compared with each other statistically. In our study, postvaccination 21st day antibody level of group R was 0.68 IU/ml (IQR: 0.79), while the same for group R+Td was 0.52 IU/ml (IQR: 0.48) (p=0.022). Concurrent administration of Td vaccine was found to have a significant negative effect on the antibody response to rabies vaccine. Our results should be confirmed with further studies including more cases.

Safety of repeated doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in adults and adolescents.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Cost effectiveness of a practice-based intervention to improve vaccination rates in adults less than 65-years-old.

The cost-effectiveness of the 4 Pillars™ Practice Transformation Program to improve vaccination rates in adults <65-years-old is unknown. Two vaccines, influenza and Tdap (tetanus, diphtheria, acellular pertussis), were targeted for this age group. Cost-effectiveness of the intervention compared with control, with a primary outcome of cost per quality adjusted life year (QALY) gained, was estimated from societal and third party payer perspectives over a 10-year time horizon using a decision analysis model. Vaccination rates and intervention costs were derived from an intervention trial, and vaccine effectiveness, illness rates, and costs with/without vaccination were obtained from US databases and literature data. Future costs and effectiveness were discounted at 3%/year. The intervention cost was $1.78 per eligible patient/year. From the societal perspective, per patient total vaccination and illness costs with the intervention were $27.43 higher than control while gaining 0.00087 QALYs, costing $31,700/QALY gained. The intervention, extrapolated to the US population, could prevent 4.2 million cases, 87,489 hospitalizations, and 5,680 deaths due to influenza over 10 y in adults <65-years-old. In a probabilistic sensitivity analysis, the intervention was favored in 68.2% of model runs at a $50,000/QALY level and in 94.3% at $100,000/QALY. In a separate scenario analysis, the intervention became cost saving if influenza economic burden was >$2,099 per case (societal base case $846). Thus, the 4 Pillars Practice Transformation Program is an economically reasonable intervention to improve vaccination rates in adults <65-years-old, and could have a substantial public health impact.

Impact of vaccine mandate on Tdap vaccination coverage among Illinois students 2014-15.

In response to recent pertussis resurgence, a multi-agency recommendation that students receive a one-time Tdap vaccine was introduced. Post mandate there was sequential increase in the Tdap vaccine uptake in the targeted population.

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

BACKGROUND/PURPOSE: A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. METHODS: Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. RESULTS: A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. CONCLUSION: The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus.

Using the 4 Pillars™ Practice Transformation Program to increase adult Tdap immunization in a randomized controlled cluster trial.

INTRODUCTION: National adult Tdap vaccination rates are low, reinforcing the need to increase vaccination efforts in primary care offices. The 4 Pillars™ Practice Transformation Program is an evidence-based, step-by-step guide to improving primary care adult vaccination with an online implementation tracking dashboard. This study tested the effectiveness of an intervention to increase adult Tdap vaccination that included the 4 Pillars™ Program, provider education, and one-on-one coaching of practice-based immunization champions. METHODS: 25 primary care practices participated in a randomized controlled cluster trial (RCCT) in Year 1 (6/1/2013-5/31/2014) and a pre-post study in Year 2 (6/1/2014-1/31/2015). Baseline year was 6/1/2012-5/31/2013, with data analyzed in 2016. Demographic and vaccination data were derived from de-identified electronic medical record (EMR) extractions. The primary outcomes were vaccination rates and percentage point (PP) changes/year. RESULTS: The cohort consisted of 70,549 patients ⩾18years who were seen in the practices ⩾1 time each year, with a baseline mean age=55years; 35% were men; 56% were non-white; 35% were Hispanic and 20% were on Medicare. Baseline vaccination rate averaged 35%. In the Year 1 RCCT, cumulative Tdap vaccination increased significantly in both intervention and control groups; in both cities, the percentage point increases in the intervention groups (7.7 PP in Pittsburgh and 9.9 PP in Houston) were significantly higher (P<0.001) than in the control groups (6.4 PP in Pittsburgh and 7.6 PP in Houston). In the Year 2 pre-post study, in both cities, active intervention groups increased rates significantly more (6.2 PP for both) than maintenance groups (2.2 PP in Pittsburgh and 4.1 PP in Houston; P<0.001). CONCLUSIONS: An intervention that includes the 4 Pillars™ Practice Transformation Program, staff education and coaching is effective for increasing adult Tdap immunization rates within primary care practices. Clinical Trial Registry Name/Number: NCT01868334.

National and State-Specific Td and Tdap Vaccination of Adult Populations.

INTRODUCTION: The Advisory Committee on Immunization Practices recommends a single dose of tetanus, diphtheria, and acellular pertussis vaccine (Tdap) for adults followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter. This study assessed recent Td and Tdap vaccination among adult populations. METHODS: The 2013 Behavioral Risk Factor Surveillance System data were analyzed in 2015 to assess Td and Tdap vaccination coverage among adults at national and state levels. Multivariable logistic regression and predictive marginal models were performed to identify factors independently associated with vaccination. RESULTS: Overall, national vaccination coverage among adults aged ≥18 years for Td was 57.5% and for Tdap was 28.9%. Among states, Td vaccination coverage ranged from 47.8% in Nevada to 73.1% in Minnesota, and Tdap coverage ranged from 17.7% in Mississippi to 47.6% in Minnesota. Characteristics independently associated with an increased likelihood of Tdap vaccination among adults aged ≥18 years were younger age; being female; American Indian/Alaska Native race; being never married; higher education; not being in the workforce; reporting a household income ≥$75,000; living in the West or Midwest U.S.; reporting excellent, very good, good, or fair health; having health insurance; having a healthcare provider; having a routine checkup in the previous year; receipt of influenza vaccination in the previous year; and having ever received pneumococcal vaccination. CONCLUSIONS: By 2013, Td and Tdap vaccination coverage were 57.5% and 28.9%, respectively. Coverage varied by state. Implementation of evidence-based programs is needed to improve Td and Tdap vaccination levels among adult populations.

Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates.

Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results suggested that cellular mechanisms right after antigen exposure should be investigated more closely to identify possible mechanisms of immunosuppression from PFAS.

Bone erosion and subacromial bursitis caused by diphtheria-tetanus-poliomyelitis vaccine.

Revaxis(®) is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare. We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature.