Exploring Perceptions and Practices Regarding Adult Vaccination against Seasonal Influenza, Tetanus, Pneumococcal Disease, Herpes Zoster and COVID-19: A Mixed-Methods Study in Greece.

We aimed to document vaccination coverage for five vaccines, predictors of each vaccine's uptake and attitudes regarding adult vaccination. Adults visiting four pharmacies were randomly invited to participate during summer 2022. Among 395 participants (mean age 51.2 years, range 19-96), vaccination rates were 78.1% for influenza and 25.8% for herpes zoster (≥60 years old), 64.3% for pneumococcal disease (≥65 years old), 33.1% for tetanus, while 11.4% had received two and 74.8% ≥3 COVID-19 vaccine doses. Half of participants (50.1%) voiced some degree of hesitancy, and 1.3% were refusers. The strongest predictor of each vaccine's uptake was doctor's recommendation (OR range 11.33-37.66, p < 0.001) and pharmacist's recommendation (4.01-19.52, p < 0.05), except for the COVID-19 vaccine, where the Attitude Towards Adult VACcination (ATAVAC) value of adult vaccination subscale's score was the only predictor (OR: 5.75, p < 0.001). Regarding insufficient coverage, thematic content analysis revealed seven main themes. Insufficient knowledge, the absence of health professionals' recommendation, perception of low susceptibility to disease, negligence and dispute of vaccine effectiveness were universal themes, whereas safety concerns and distrust in authorities were reported solely for COVID-19 vaccination. Designing public interventions aiming to increase trust in adult vaccination is essential in the aftermath of the COVID-19 pandemic. Health professionals' role in recommending strongly adult vaccination is crucial.

Generalized Tetanus in an Adult Patient.

Tetanus is a vaccine-preventable disease that commonly occurs in under-resourced countries; clinically, it manifests as spontaneous muscle spasms and overall body rigidity, which can lead to autonomic dysfunction. The diagnosis of tetanus is primarily clinical, although laboratory testing is available, treatment of a clinical case should never be delayed. Management includes general support measures, prevention of complications, control of muscle spasms, and immunoglobulin. We present a patient from an underdeveloped region with a diagnosis of generalized tetanus after injury with a disc grinder. Clinical presentation of the patient, diagnostic studies performed, management, and outcome are discussed.

Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece.

OBJECTIVES: Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. STUDY DESIGN: This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. METHODS: A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. RESULTS: Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52-8.14], pneumococcal disease: 15.73 [10.98-22.52], HZ: 17.01 [9.05-31.96], tetanus: 23.93 [16.20-35.35], measles: 33.47 [16.85-66.47], and hepatitis B: 73.92 [17.47-312.74]). Being well-informed about each vaccine was also a predictor of its uptake. CONCLUSIONS: Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage.

Collaborative study for the calibration of a replacement International Standard for tetanus toxoid for use in flocculation test.

Here we report the results of a study to establish a replacement WHO International Standard (IS) for tetanus toxoid for use in flocculation test. The standard was calibrated in flocculation units (Lf) against the 2nd IS using the Ramon flocculation method. At its 70th meeting in October 2019, WHO ECBS established the material (coded 16/302) as the 3rd WHO IS, with an assigned value of 970 Lf/ampoule from the results of seventeen laboratories across ten different countries. The study also provided an opportunity to assess the use of alternative methods for measuring Lf. Participants were asked to use an in-house Enzyme Linked Immunosorbent Assay (ELISA) developed at NIBSC, or other suitable in-house methods, to determine ELISA-specific Lf values (Lf-eq units are specific only for pre-calibration of antitoxin in the flocculation test) of 16/302 to compare to those of the flocculation test. Nine laboratories participated by performing the NIBSC ELISA, one laboratory performed flocculation by laser light-scattering following an in-house protocol, and three laboratories performed ELISA following in-house protocols. The results intimate that these alternative methods could be useful for monitoring consistency of production at different stages of vaccine manufacturing.

Proportion of births protected against neonatal tetanus and its associated factors among mothers who gave birth within the past 6 months in Gozamn district, Northwest Ethiopia, 2022.

Today, neonatal tetanus accounts for a significant portion of newborn and under-5 mortality - 40% and 57%, respectively - and is the most prevalent cause of neonatal mortality and morbidity, particularly in developing nations. As a result, more study on birth protection against neonatal tetanus is required because it is such a terrible condition with such a high death rate and there is a need for more recent evidence on it. From April 1 to 30, 2022, a community-based cross-sectional survey was carried out in the Gozamn district of Northwest Ethiopia. A two-stage stratified sampling procedure was applied, with an overall sample size of 831. The data were gathered using a pre-tested, structured questionnaire. It was then checked, cleaned, and entered into Epidata software version 4.6 before being exported to Stata version 14 for analysis. The proportions of birth protected against neonatal tetanus were 58.57% (95% CI (55.15-61.89%) in the study. Mother who had radio (AOR = 3.09,95%CI: 2.09, 4.56), mother who travel less than one hour to reach nearest health facility (AOR = 1.96,95%CI: 1.23,3.10), mother who gave birth of their last child in the health institution (AOR = 4.17,95%CI:2.39,7.28), mothers who had information from health professional (AOR = 2.56,95%CI:1.56,4.19) and > 4 ANC visit (AOR = 2.57,95%CI:1.55,4.26) were positive predictors of birth protected against neonatal tetanus. Low levels of maternal protection against neonatal tetanus were seen in this study location. To enhance the percentage of births protected against neonatal tetanus, professional-based guidance regarding the TT vaccine are essential.

Biomarkers detected in cord blood predict vaccine responses in young infants.

Introduction: Factors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year. Methods: Longitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures. Results: Using a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively. Discussion: Sustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.

Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria.

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.

Intramuscular injection of a mixture of COVID-19 peptide vaccine and tetanus vaccine in horse induced neutralizing antibodies against authentic virus of SARS-CoV-2 Delta variant.

Peptide vaccine is not effective due to its low immunogenicity. To improve the efficacy of peptide vaccine against COVID-19, a novel method was developed by mixing a COVID-19 peptide vaccine with a tetanus vaccine. In this study, intramuscular injection of a mixture of COVID-19 peptide vaccine and tetanus vaccine twice, i.e., first dose on day 0 and second dose on day 21, induced neutralizing antibodies against authentic virus of SARS-CoV-2 Delta variant in a horse. Horse serum of day 35, i.e., two weeks after the second dose, neutralized authentic virus of SARS-CoV-2 Delta variant, equal to half effectiveness of human serum from vaccinees of Moderna COVID-19 vaccine. However, neither horse serum nor human serum neutralized Omicron variant authentic virus. No side effects were observed after each dose. This study indicates intramuscular injection of a mixture of COVID-19 peptide vaccine and tetanus vaccine may work in humans to improve peptide vaccine efficacy against SARS-CoV-2.

Tetanus, analysis of 29 cases

BackgroundTetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions.MethodsThis is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995–2019. Epidemiological and clinical data were obtained from the patient's medical records.ResultsA total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died.DiscussionThe incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men. (AU)

IntroducciónEl tétanos es causado por Clostridium tetani, bacteria anaerobia, ubicada en el suelo. Este microorganismo penetra a través de heridas y libera neurotoxinas que bloquean la función inhibitoria, produciendo espasticidad y fracaso respiratorio. Es una enfermedad grave, especialmente en regiones empobrecidas.MétodosSerie de casos realizada en dos hospitales vigueses (área 600.000 habitantes). Los casos fueron identificados mediante los sistemas de codificación entre 1995-2019. Los datos asistenciales se obtuvieron de la historia clínica.ResultadosSe identificaron 33 casos, mediana de edad, 67 años, la mayoría mujeres (n = 16, 55,2%). El tétanos generalizado fue la forma clínica predominante, la rigidez cervical el síntoma más común. Un total de 25 pacientes requirieron ingreso en UCI, 21 ventilación mecánica, dos fallecieron.DiscusiónEl número de casos fue bajo, pero la mayoría graves. La mortalidad fue ligeramente superior a la informada previamente. La mortalidad se concentró en mujeres ancianas, concordante con otros países desarrollados, mientras que la mortalidad en regiones no-desarrolladas se agrupa en varones de mediana edad. (AU)

Tetanus, analysis of 29 cases.

BACKGROUND: Tetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions. METHODS: This is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995-2019. Epidemiological and clinical data were obtained from the patient's medical records. RESULTS: A total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died. DISCUSSION: The incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men.

Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions.

BACKGROUND: Ensuring consistency of tetanus neurotoxin (TeNT) production by Clostridium tetani could help to ensure consistent product quality in tetanus vaccine manufacturing, ultimately contributing to reduced animal testing. The aim of this study was to identify RNA signatures related to consistent TeNT production using standard and non-standard culture conditions. METHODS: We applied RNA sequencing (RNA-Seq) to study C. tetani gene expression in small-scale batches under several culture conditions. RESULTS: We identified 1381 time-dependent differentially expressed genes (DEGs) reflecting, among others, changes in growth rate and metabolism. Comparing non-standard versus standard culture conditions identified 82 condition-dependent DEGs, most of which were specific for one condition. The tetanus neurotoxin gene (tetX) was highly expressed but showed expression changes over time and between culture conditions. The tetX gene showed significant down-regulation at higher pH levels (pH 7.8), which was confirmed by the quantification data obtained with the recently validated targeted LC-MS/MS approach. CONCLUSIONS: Non-standard culture conditions lead to different gene expression responses. The tetX gene appears to be the best transcriptional biomarker for monitoring TeNT production as part of batch-to-batch consistency testing during tetanus vaccine manufacturing.

Development and validation of a targeted LC-MS/MS quantitation method to monitor cell culture expression of tetanus neurotoxin during vaccine production.

The tetanus neurotoxin (TeNT) is one of the most toxic proteins known to man, which prior to the use of the vaccine against the TeNT producing bacteria Clostridium tetani, resulted in a 20% mortality rate upon infection. The clinical detrimental effects of tetanus have decreased immensely since the introduction of global vaccination programs, which depend on sustainable vaccine production. One of the major critical points in the manufacturing of these vaccines is the stable and reproducible production of high levels of toxin by the bacterial seed strains. In order to minimize time loss, the amount of TeNT is often monitored during and at the end of the bacterial culturing. The different methods that are currently available to assess the amount of TeNT in the bacterial medium suffer from variability, lack of sensitivity, and/or require specific antibodies. In accordance with the consistency approach and the three Rs (3Rs), both aiming to reduce the use of animals for testing, in-process monitoring of TeNT production could benefit from animal and antibody-free analytical tools. In this paper, we describe the development and validation of a new and reliable antibody free targeted LC-MS/MS method that is able to identify and quantify the amount of TeNT present in the bacterial medium during the different production time points up to the harvesting of the TeNT just prior to further upstream purification and detoxification. The quantitation method, validated according to ICH guidelines and by the application of the total error approach, was utilized to assess the amount of TeNT present in the cell culture medium of two TeNT production batches during different steps in the vaccine production process prior to the generation of the toxoid. The amount of TeNT generated under different physical stress conditions applied during bacterial culture was also monitored.

Organ transplantation and vaccination / 器官移植

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.

Regional disparities and their contribution to the coverage of the tetanus toxoid vaccine among women aged 15-49 years in Indonesia.

Background: The prevention of Clostridium tetani bacterial infection through the administration of the tetanus toxoid (TT) vaccine in women is important. The purpose of this study was to determine the regional disparities and factors associated with TT vaccine coverage in women aged 15-49 years in Indonesia. Methods: The Indonesian Demographic Health Survey (IDHS) 2017 data was used in this study. A total of 36,028 women, aged 15-49 years were recruited using the two-stage stratified cluster sampling technique. The questionnaire used was based on the DHS Questionnaire Phase 7. Chi-squared and binary logistic regression were used in this study as part of the analysis. Results: We found that the TT vaccine coverage was 75.32% and that the majority were spread across several provinces. The provinces of Bali and Nusa Tenggara, the richer respondents, living in a rural area, visiting the health facility, having health insurance, and those currently working were factors making it more likely that the women would receive the TT vaccine. The respondents aged 15-24 years with a primary education level and the respondents who were divorced were less likely to receive the TT vaccine. Conclusion: The coverage of the TT vaccine among women can be increased by considering the regional disparities in Indonesia and the socio-economic demographic details of the respondents. Strengthening the policies from the central government in the local governments can improve the screening process and vaccine delivery outcomes. In addition, the importance of giving the TT vaccine to women needs to be relayed through health education in collaboration between health workers and the public.

Adrenal Crisis Secondary to Influenza and Tetanus Vaccination in an Adult Without Known Adrenal Insufficiency: A Case of Autoimmune Adrenalitis.

Adrenal crisis (AC) is a rare but known life-threatening condition in patients with adrenal insufficiency (AI). We report the case of a 21-year-old without known AI who developed AC after routine vaccinations. Workup revealed that the patient had underlying, undiagnosed autoimmune adrenalitis. This is the first report of AC induced by influenza and diphtheria, tetanus, and acellular pertussis (DTaP) vaccinations in a patient without known AI.

Secondary metabolite and antipyretic effects of Maja (Crescentia cujete L.) in fever-induced mice.

OBJECTIVES: Fever is a condition when the body experiences an increase in average body temperature above normal level. Maja fruit (Crescentia cujete L.) contains chemical compounds including alkaloid, flavonoid, saponin, and terpenoid, suspected as potential antipyretics. METHODS: The study aimed to determine the antipyretic activity of ethanol extract of Maja fruit. A total of 25 male white mice of the DDY strain (20-30 g). These treatments divided into three groups with a dose extract of 125, 250, 500 mg/kg BW, standard groups of ibuprofen 400 mg/kg BW, and control groups of CMC-Na 1%. Mice were injected intraperitoneally with 0.1 cc of DPT vaccine-induced. Observations were made by measuring the rectal temperatures of mice using a digital thermometer before DPT vaccine injected or average temperatures, at 0 min (after DPT vaccine injected), 60, 120, 180, and 240 min after administering the test material. The differences between the positive control group, test group, and the negative control group were compared using statistical analysis using one-way variance analysis (ANOVA). The results were considered statistically when the value is (p<0.05). RESULTS: The above phytochemical screening results showed that alkaloids, flavonoids, and saponins were present in the Maja fruit powder and extract (C. cujete L.). Based on the results of the statistical analysis obtained, i.e., Group II was not significantly different from Group III and Group IV (p≤0.05) and was significantly different from Group I and Group V. Group I was significantly different from Group II, Group III and Group IV and was not significantly different from Group V (p≥0.05). CONCLUSIONS: The study showed that Maja fruit mice's antipyretic behavior at doses of 125, 250, and 500 mg/kg BW was confirmed as a result in reducing the body temperature of male mice. The 500 mg/kg BW dosage of Maja fruit extract (C. cujete L) effectively reduced fever.

Factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal.

BACKGROUND: Vaccination during pregnancy can protect pregnant women and their babies from infectious diseases. Tetanus vaccine, also known as tetanus toxoid, is the only vaccine given to pregnant women in The Gambia and Senegal, where it is given by antenatal care providers as part of the Expanded Programme on Immunization. A qualitative study was undertaken to explore factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal. METHODS: Focus group discussions and in-depth interviews were conducted across urban and rural settlements of The Gambia and Senegal. We explored the knowledge, attitudes, and perceptions of 152 women who were either pregnant or with an infant. NVivo 11 Qualitative Data Analysis Software was used for management and thematic analysis of the data. RESULTS: Women had sufficient knowledge of the need for tetanus vaccine from different information sources but insufficient knowledge of tetanus causes, signs and symptoms. Tetanus vaccine was perceived to be safe and side effects such as pain and swelling at site of injection did not deter uptake of future doses. Women overall had confidence in their sources of vaccine information and the health care workers who administered maternal vaccinations. Their willingness to accept vaccination during pregnancy was particularly influenced by their husbands and trusted healthcare workers. Women across all sites mentioned they would accept new maternal vaccines if they are sensitized beforehand about any potential risks and benefits to them and their babies. CONCLUSION: Vaccine acceptance can be influenced by several factors including contextual, individual or group influences and vaccine or vaccination-specific issues. Women across The Gambia and Senegal are generally vaccine acceptors with confidence in the health care workers who vaccinate them and few concerns about maternal vaccines. Women's acceptance of vaccination during pregnancy is based on previous vaccination experiences and individual weighing of risks and benefits.

Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double-Blind, Dose Escalation, Placebo- and Positive-Controlled, Phase 1/2 Trial.

Tetanus is a fatal but vaccine-preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)-based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double-blind, dose escalation, placebo- and positive-controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT-Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT-Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment-related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen-specific CD4+/CD8+ T-cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.

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.

Incorporation of T-cell epitopes from tetanus and diphtheria toxoids into in-silico-designed hypoallergenic vaccine may enhance the protective immune response against allergens.

OBJECTIVES: New generation of allergy vaccines is capable of promoting the development of protective IgG and blocking the functionality of allergen-specific IgE. We incorporated universal and powerful T-cell epitopes from tetanus and diphtheria toxoids (TD epitope) into recombinant Che a 2, the well-known allergic profilin of Chenopodium album, to determine its immunological properties. MATERIALS AND METHODS: The sequence and accordingly the structure of the recombinant Che a 2 was altered to generate a hypoallergenic variant (rChe a 2.rs). Moreover, TD epitope was incorporated to produce a novel vaccine that was nominated as rChe a 2.rsT.D. The effect of treatment with these variants was evaluated on the generation of allergen-specific IgG class, as well as lymphocyte proliferation in mice. Moreover, IgE-binding characteristics of the allergic patients' sera were determined by ELISA and proliferation and cytokine production was measured in T-cells. RESULTS: ELISA and dot blot revealed strong reduction of the IgE-reactivity of human sera to the variants of Che a 2 as compared to the wild-type molecule. Furthermore, Che a 2.rs and Che a 2.rsT.D induced much lower levels of IL5 and IL13 secretion from allergic patients' PBMCs in comparison to wild-type Che a 2 protein. In mice, rChe a 2.rsT.D induced high titers of Che a 2-specific IgG antibody capable of blocking IgE-binding to rChe a 2 and induced lymphocyte proliferation more potently than rChe a 2.rs. CONCLUSION: Collectively, incorporation of T-cell epitopes of tetanus and diphtheria into hypoallergenic vaccines can dramatically enhance anti-allergic immune mechanisms, particularly in poor responders.