Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.
Artificial Intelligence ; Data Warehousing ; Humans ; Tetanus ; Tetanus Toxoid ; Whooping Cough/prevention & control*

BACKGROUND: Incidence of whooping cough is increasing in Korea. Since 2011, occurrence among adolescents and adults has risen putting vulnerable neonates at risk. National immunization guidelines now include Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during pregnancy and as a cocooning strategy (i.e., vaccinating adults and adolescents in contact with neonates). This study assessed post-marketing Tdap (Boostrix®, GSK, Belgium) vaccine safety in subjects ≥ 10 years. METHODS: This open, non-comparative multi-center study was conducted over six years at 10 hospitals in Korea. Subjects received Tdap in normal clinical practice according to local prescribing information. All adverse events (AEs) were recorded, classified as expected or unexpected, and severity and relationship to Tdap were assessed. RESULTS: The analysis included 672 Korean subjects (mean age, 44 years; range, 11–81), 451 were women and 211 were pregnant. Ninety subjects experienced 124 AEs (incidence 13.39%) of which six were serious AEs (SAEs) assessed as not related to vaccination, and 51 were non-SAEs related to vaccination (mostly administration site reactions). Overall 65/124 AEs were unexpected; the most common were 14 constipation, 5 dyspepsia, 4 common cold and 4 premature labor cases. One case of common cold was assessed as possibly related to vaccination. Pregnancy outcome was ‘live infant, no apparent congenital anomaly’ in 195 subjects (92.42%) or ‘lost to follow-up’ in 16 subjects. CONCLUSION: Tdap administration to Korean subjects ≥ 10 years, including pregnant women, for the prevention of diphtheria, tetanus and pertussis was shown to have a well-tolerated safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01929291
Adolescent ; Adult ; Common Cold ; Constipation ; Diphtheria Toxoid ; Diphtheria ; Dyspepsia ; Female ; Humans ; Immunization ; Incidence ; Infant ; Infant, Newborn ; Korea ; Obstetric Labor, Premature ; Pregnancy ; Pregnancy Outcome ; Pregnant Women ; Prospective Studies ; Tetanus Toxoid ; Tetanus ; Vaccination ; Whooping Cough

PURPOSE: Despite effectiveness and safety of maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, Tdap vaccination coverage during pregnancy remains quite low. We assessed the knowledge, attitude and practice on maternal Tdap vaccination among pregnant women. METHODS: This study was a cross-sectional survey of pregnant women who visited tertiary obstetrics and gynecologic units in Seoul and Gyeonggi province of Korea. Individual questionnaires were administered to assess knowledge, attitude and practice on maternal immunization with Tdap. RESULTS: The questionnaires were completed by 184 pregnant women; 158 (86%) had not received information from doctors about pertussis and Tdap, and 166 (90%) did not know the need for Tdap vaccination. Only 7% of pregnant women unlikely to receive Tdap vaccine during current pregnancy answered 3 or more of the 5 knowledge-based questions correctly. By logistic regression analysis, recommendation by doctor (adjusted odd ratio [OR], 236.2; 95% confidence interval [CI], 12.6–4,432), belief that the vaccine is effective (adjusted OR, 40.21; 95% CI, 2.35–687.7), and belief that the vaccine is safe (adjusted OR, 19.83; 95% CI, 1.54–255.9) were significantly important factors to respondents’ intention to be vaccinated. CONCLUSIONS: Most pregnant women seem to be neither recommended nor adequately informed about Tdap vaccination. Information given by health care professionals is very important to increase Tdap coverage among pregnant women.
Cross-Sectional Studies ; Delivery of Health Care ; Diphtheria Toxoid ; Diphtheria ; Female ; Gyeonggi-do ; Humans ; Immunization ; Intention ; Korea ; Logistic Models ; Obstetrics ; Pregnancy ; Pregnant Women ; Seoul ; Tetanus Toxoid ; Tetanus ; Vaccination ; Whooping Cough

OBJECTIVES: Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines. METHODS: Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay. RESULTS: All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay. CONCLUSION: Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency.
Adult* ; Antitoxins ; Bacterial Infections ; Child ; Diphtheria Toxoid ; Diphtheria* ; Humans ; Tetanus Toxoid* ; Tetanus* ; Toxoids ; Vaccination ; Vaccines* ; Whooping Cough

In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone.
Animals ; Bordetella pertussis* ; Bordetella* ; Diphtheria Toxoid ; Diphtheria* ; Enzyme-Linked Immunosorbent Assay ; Lung ; Mice* ; Neutralization Tests ; Tetanus Toxoid* ; Tetanus* ; Vaccines ; Whooping Cough

PURPOSE: Recombinant subunit vaccines provide safe and targeted protection against microbial infections. However, the protective efficacy of recombinant subunit vaccines tends to be less potent than the whole cell vaccines, especially when they are administered through mucosal routes. We have reported that a bacterial flagellin has strong mucosal adjuvant activity to induce protective immune responses. In this study, we tested whether FlaB could be used as a fusion partner of subunit vaccine for tetanus. MATERIALS AND METHODS: We constructed fusion proteins consisted with tetanus toxin fragment C (TTFC), the nontoxic C-terminal portion of tetanus toxin, and a Toll-like receptor 5 agonist from Vibrio vulnificus (FlaB). Mice were intranasally administered with fusion protein and protective immune responses of the vaccinated mice were analyzed. RESULTS: FlaB-TTFC recombinant protein induced strong tetanus-specific antibody responses in both systemic and mucosal compartments and prolonged the survival of mice after challenge with a supra-lethal dose of tetanus toxin. CONCLUSION: This study establishes FlaB as a successful fusion partner for recombinant subunit tetanus vaccine applicable through mucosal route, and it further endorses our previous observations that FlaB could be a stable adjuvant partner for mucosal vaccines.
Animals ; Antibody Formation ; Flagellin* ; Mice ; Tetanus ; Tetanus Toxin* ; Tetanus Toxoid ; Toll-Like Receptor 5 ; Vaccines ; Vaccines, Subunit ; Vibrio vulnificus

PURPOSE: The objective of this study was to assess and investigate the epidemiology of pertussis in infants under 6 months of age. METHODS: A prospective study was conducted between October 1, 2011 and April 30, 2013 in CHA Bundang Medical Center, Seongnam, South Korea. Polymerase chain reaction (PCR) or culture was used to detect Bordetella pertussis in nasopharyngeal aspirates from case patients who were hospitalized for acute lower respiratory tract infection (LRTI). In addition, multiplex real-time PCR assays were also performed to detect 6 etiologic viruses, including adenovirus, human metapeumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus and rhinovirus. RESULTS: Of the 79 enrolled case patients, whose median age was 2 months of age, the most common diagnoses uncovered in this study were acute bronchiolitis (60%) and pneumonia (28%). B. pertussis infection was found in 13 cases (16%), in which 7 (53%) was coinfected with respiratory syncytial virus and 1 (7%) with influenza A virus. Of the 13 patients with B. pertussis infection, 6 (46%) were not vaccinated with the diphtheria, tetanus toxoid, and acellular pertussis vaccine, while 6 (46%) received 1 dose, and 1 (8%) received 2 doses. CONCLUSION: B. pertussis infection was present in 16% of under 6 month-old infants, who were hospitalized for acute LRTI. Therefore, a nationwide epidemiological surveillance of pertussis, including institutions that cater to infants under 6 months of age is necessary and needed.
Adenoviruses, Human ; Bordetella pertussis ; Bronchiolitis ; Diagnosis ; Diphtheria ; Epidemiology ; Gyeonggi-do ; Humans ; Infant* ; Influenza A virus ; Korea ; Orthomyxoviridae ; Paramyxoviridae Infections ; Pertussis Vaccine ; Pneumonia ; Polymerase Chain Reaction ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Respiratory Syncytial Viruses ; Respiratory Tract Infections ; Rhinovirus ; Tetanus Toxoid ; Vaccination ; Whooping Cough*

This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-gamma(IFN-gamma) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, Fib-alpha R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-gamma or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.
Animals ; Arthritis, Rheumatoid ; Candida albicans ; Cytokines ; Epitopes, T-Lymphocyte ; Fibrinogen ; HLA-DR4 Antigen ; Humans ; Interleukin-17 ; Mice ; Mice, Transgenic ; Mycobacterium tuberculosis ; Peptides ; T-Lymphocytes ; Tetanus Toxoid

No abstract available.
Aged ; Anti-Infective Agents/therapeutic use ; Drug Therapy, Combination ; Foot Injuries/*complications ; Humans ; Male ; Muscle Relaxants, Central/therapeutic use ; Tetanus/diagnosis/drug therapy/*microbiology ; Tetanus Toxoid/therapeutic use ; Treatment Outcome ; Trismus/diagnosis/drug therapy/*microbiology ; Wounds, Stab/*complications

BACKGROUND: Improvement of additional immunization rate is indicated as an important factor for effective immunization of diseases. In this study, the relationship between retention of mother and child health handbook and additional immunization rate of Japanese encephalitis and tetanus was examined. METHODS: A survey via questionnaire was performed against parents of students of middle schools in Gwangmyeong-si, Gyeonggi-do, and elementary schools in Seoul. Among 350 copies of the questionnaire delivered via post mail, 261 copies were collected and used in the analysis. The questionnaire included general features of subjects and their children, retention of the mother and child health handbook, and recognition of additional immunization of the Japanese encephalitis and tetanus vaccine. RESULTS: It was found that 80.8% of subjects answered affirmative to retaining the mother and child health handbook, and the group retaining the handbook had higher recognition rate of the need for additional immunization than the group that did not, for the Japanese encephalitis vaccine (83.2% vs. 51.2%, P < 0.001) and for the tetanus vaccine (66.5% vs. 31.7%, P < 0.001). Although the group retaining the handbook had a significantly higher additional immunization rate of the tetanus vaccine of 48.6% vs. 17.1% (P = 0.001), the immunization rate of the Japanese encephalitis vaccine did not show a significant difference (P = 0.231). The group recognizing the need for additional immunization of the Japanese encephalitis and tetanus vaccine had a significantly higher additional immunization rate than the counterpart (P < 0.001). CONCLUSION: It was considered that retention of the mother and child health handbook was related to recognition and execution of additional immunizations.
Asian Continental Ancestry Group ; Child ; Child Health ; Coat Protein Complex I ; Encephalitis, Japanese ; Humans ; Immunization ; Mothers ; Parents ; Postal Service ; Retention (Psychology) ; Tetanus ; Tetanus Toxoid ; Surveys and Questionnaires