Objective: To identify and analyze two strains of C. diphtheriae in Guangdong Province by combining whole genome sequencing with traditional detection methods. Methods: The C. diphtheriae was isolated from Guangzhou in 2010 and Zhuhai in 2020 respectively. Isolates were identified by API Coryne strips and MALDI-TOF-MS. Genomic DNA was sequenced by using Illumina. The assembly was performed for each strain using CLC software. J Species WS online tool was used for average nucleoside homology identification, then narKGHIJ and tox gene were detected by NCBI online analysis tool BLSATN. MEGA-X was used to build a wgSNP phylogenetic tree. Results: GD-Guangzhou-2010 was Belfanti and GD-Zuhai-2020 was Gravis. ANIb between GD-Guangzhou-2010 and C. belfantii was 99.61%. ANI between GD-Zhuhai-2020 and C. diphtheriae was 97.64%. BLASTN results showed that the nitrate reduction gene narKGHIJ and tox gene of GD-Guangzhou-2010 was negative, while GD-Zhuhai-2020 nitrate reduction gene narKGHIJ was positive. There were two obvious clades in wgSNP phylogenetic tree. The first clades included all Mitis and Gravis types strains as well as GD-Zhuhai-2020. The second clades contained all isolates of C.belfantii, C.diphtheriae subsp. lausannense and GD-guangzhou-2010. Conclusion: Two non-toxic C. diphtheriae strains are successfully isolated and identified. The phylogenetic tree suggests that GD-Guangzhou-2010 and GD-Zhuhai-2020 are located in two different evolutionary branches.
China/epidemiology* ; Corynebacterium ; Corynebacterium diphtheriae/genetics* ; Diphtheria/microbiology* ; Humans ; Nitrates ; Phylogeny

There is a rare case of an elderly diabetic with diabetic foot infection at Hainan General Hospital in September 2021, which was diagnosed as Corynebacterium diphtheriae infection incidentally on routine culture with conventional methods and molecular biological approaches, to aid in diagnosis in clinical practice. Owing to smear staining, Albert staining and VITEK 2 system, automated identification systems viz matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) confirmed combing with 16S ribosomal RNA (16S rRNA) gene has been used for the taxonomic classification of bacteria. Otherwise, toxin gene tox was done for diphtheria toxin synthesis. The isolate was Gram-stain-positive, rod-like arrangement with irregular thickness, with characteristic metachromatic granules, ferment most sugars and homology of 16S rRNA analyses with C. diphtheriae NCTC11397^T (MW682323.1) was greater than a 100% possibility, toxin gene tox was negative. The findings lay the foundation to clinical identify and trace of non-toxigenic C. diphtheriae. Moreover, this work provides insights into the non-toxigenic C.diphtheriae that contribute to recognized risk of non-toxigenic C.diphtheriae infections.
Aged ; Corynebacterium/genetics* ; Corynebacterium diphtheriae/genetics* ; Diabetes Mellitus ; Diabetic Foot ; Diphtheria/microbiology* ; Humans ; RNA, Ribosomal, 16S/genetics*

HPV vaccination is the most effective way for preventing the cervical cancer. To respond the WHO calling for cervical cancer elimination, some Chinese provincial governments are launching the Free HPV Vaccination Programs for teenagers. Basing on the current stage of domestic utilization and the global immunization strategies of HPV vaccination, this paper provides a comprehensive review of the key aspects in the process of HPV vaccination, including subjects and priority vaccination population, vaccination dose and time interval, the principal of vaccination replacement, and the vaccination suggestion on special populations, etc. The article above contents and gives the advice on the immunization strategy of HPV vaccination in China.
AIDS Vaccines ; Adolescent ; BCG Vaccine ; China ; Diphtheria-Tetanus-Pertussis Vaccine ; Female ; Humans ; Immunization Programs ; Influenza Vaccines ; Measles-Mumps-Rubella Vaccine ; Papillomavirus Infections/prevention & control* ; Papillomavirus Vaccines ; Respiratory Syncytial Virus Vaccines ; SAIDS Vaccines ; Uterine Cervical Neoplasms ; Vaccination

Objective: To analyze the dropout of adsorbed diphtheria, tetanus and acellular pertussis combined vaccine (DTaP) routine immunization in China in 2019. Methods: DTaP vaccination data in all counties in China were collected through National Immunization Program Information Management System in 2019. Cumulative dropout rate and vaccination rate of DTaP in different provinces were calculated. According to the P₂₅, P₅₀ and P₇₅ values of DTaP dropout rate for all counties by province, counties in each province were divided into four groups (Q₁-Q₄). The DTaP average dropout rate of four groups and absolute difference (difference in DTaP average dropout rate between Q₄ and Q₁) were calculated. Spearman rank correlation was used to analyze the relationship between absolute difference and provincial DTaP dropout rate, DTaP₁ and DTaP₃ vaccination rate. Results: DTaP₁ vaccination rate ranged from 92.98% to 99.94% by province, with a median of 99.55%. Provincial DTaP dropout rate ranged from 0.36% to 28.66%, with a median of 3.54%. The provincial DTaP dropout rate was more than 10% in Gansu and Guizhou, about 28.66% and 17.19%. Absolute difference ranged from 4.02% to 39.22%, with a median of 10.16%. Provinces with the largest absolute difference were Gansu, Qinghai, Liaoning and Guizhou, about 39.22%, 34.48%, 23.31% and 21.33%, respectively. Correlation analysis indicated that the absolute difference was positively correlated with provincial DTaP dropout rate, with a correlation coefficient of 0.492 (P=0.004). It was negatively correlated with DTaP₁ and DTaP₃ vaccination rate. Correlation coefficients were -0.542 (P=0.001) and -0.562 (P=0.001), respectively. Conclusions: There are significant county-level differences in DTap dropout rate in most provinces, with relatively high difference in western provinces.
Humans ; Infant ; Whooping Cough/prevention & control* ; Diphtheria-Tetanus-Pertussis Vaccine ; Diphtheria-Tetanus-acellular Pertussis Vaccines ; Vaccination ; China ; Immunization, Secondary ; Immunization Schedule ; Antibodies, Bacterial

Diphtheria toxin is an ADP-ribosyltransferase toxic to human cells. Mutation of the active site in its catalytic domain eliminates the toxicity, but retains its immunogenicity. A non-toxic mutant of diphtheria toxin known as CRM197 protein has become an ideal carrier protein for conjugate vaccines. CRM197 can further improve its immunogenicity by cross-linking with other antigens, so it has good potential to find broad applications. Unfortunately, inclusion bodies are easily formed during the expression of recombinant CRM197 protein in Escherichia coli, which greatly reduces its yield. In order to address this problem, pG-KJE8 vector carrying molecular chaperones and plasmid pET28a-CRM197, were co-expressed in Escherichia coli. The results showed that the recombinant CRM197 protein was successfully expressed and appeared largely in inclusion bodies. The molecular chaperones DnaK, DnaJ, GrpE, GroES and GroEL5 expressed can facilitate correct and rapid folding of CRM197. Furthermore, it can also improve the recovery rate of soluble CRM197 protein. The soluble expression of CRM197 was maximized upon addition of 1.0 mmol/L IPTG, 0.5 mg L-arabinose, 5.0 ng/mL tetracycline and induction at 20oC for 16 h. The soluble CRM197 protein shows good immunoreactivity, demonstrating the molecular chaperones expressed from pG-KJE8 facilitated the soluble expression of CRM197 protein in E. coli.
Bacterial Proteins ; Diphtheria Toxin/genetics* ; Escherichia coli/genetics* ; Humans ; Molecular Chaperones/genetics* ; Recombinant Proteins/genetics*

An increase in the number of patients with infectious diseases in Korea, can be attributed to various factors, such as the prevalence of new infectious diseases of the 21st century, the re-emergence of past infectious diseases, an increase in the number of elderly individuals, patients with chronic diseases, immune deficiency, and globalization. In this context, vaccination becomes vital for the adult population. Although, the guidelines for adult immunization are currently being updated, the rate of adult vaccination remains lower than that of infant vaccination. At present, the major challenges for increasing the rate of adult immunization include negative views on the need for some immunizations and a lack of understanding of group immunity among the youth. Consequently, a successful immunization program will be required to direct efforts towards educating patients and spreading awareness. Based on the current guidelines and practical applications, varicella zoster; Japanese encephalitis; tetanus, diphtheria, and pertussis; pneumococcus; measles, mumps, and rubella; and hepatitis A vaccines could effectively be considered for adult vaccination.
Adolescent ; Adult ; Aged ; Chickenpox ; Chronic Disease ; Communicable Diseases ; Diphtheria ; Encephalitis, Japanese ; Hepatitis A Vaccines ; Herpes Zoster ; Humans ; Immunization Programs ; Immunization ; Infant ; Internationality ; Korea ; Measles ; Mumps ; Pneumococcal Vaccines ; Prevalence ; Rubella ; Streptococcus pneumoniae ; Tetanus ; Vaccination ; Whooping Cough

PURPOSE: There is no standard method for confirming the immunogenicity of acellular pertussis vaccines. We tried to develop a local standard method for evaluating the immunogenicity of the three-component of acellular pertussis vaccines which was developed by a Korean local company. MATERIALS AND METHODS: The developed pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) were evaluated by in-house enzyme-linked immunosorbent assay (ELISA) using 189 negative sera, 25 positive sera, and 73 paired sera (pre- and post-Tdap [tetanus, diphtheria, and acellular pertussis] vaccinated sera). ELISA units were calculated by the reference line method, compared with World Health Organization reference sera, and the cut-off value was calculated using negative sera. RESULTS: When compared to National Institute for Biological Standards and Control control antigen (NIBSC) control antigens, the developed pertussis toxin (PT) and filamentous haemagglutinin (FHA) antigens were 203.48 and 61.60 IU/µg, respectively. Each in-house ELISA was established by validating the coefficients of variation % (PT, 11.53%; FHA, 8.60%; pertactin [PRN], 9.86%) obtained from the results of inter- and intra-assay variation. Also, the cut-off values of PT, FHA, and PRN were 11.65, 38.95, and 5.66 EU/mL, respectively. The distributions of antibody levels in paired showed that 93.15% (68/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were higher than a 100% increase after vaccination. Additionally, the values of 89.04% (65/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were below each cut-off point. CONCLUSION: We established an in-house ELISA method using self-developed antigens, and these immunoassays have provided a way to standardize measuring the immunogenicity of newly developed vaccines, through single- and dual-serology.
Diphtheria ; Enzyme-Linked Immunosorbent Assay ; Hemagglutinins ; Immunoassay ; Immunoglobulin G ; Korea* ; Methods* ; Pertussis Toxin ; Pertussis Vaccine ; Vaccination ; Vaccines* ; Whooping Cough* ; World Health Organization

BACKGROUND: This study was conducted to assess the immunogenicity and safety of GC1107 (adult tetanus diphtheria [Td] vaccine). The primary goal was to evaluate the non-inferiority of the immunogenicity of GC1107 compared to the control vaccine. Additionally, the safety profiles of GC1107 and the control vaccine were compared. METHODS: The subjects were adults ≥ 18 years old who were not injected with Td or adult tetanus-diphtheria-pertussis (TdaP) vaccine within the recent 5 years. A total of 253 subjects were enrolled and randomized to either the GC1107 group or the control group. For immunogenicity assessment, blood samples were collected at baseline and 28 days after vaccination and antibody titer of diphtheria and tetanus were assessed. RESULTS: The seroprotection rates of diphtheria and tetanus were 89.76% and 91.34%, respectively, in the GC1107 group, and 87.80% and 86.99% in the control group. The geometric mean titer (GMT) of the anti-diphtheria antibody increased after vaccination in both groups, showing no significant difference between the groups (P = 0.139). The anti-tetanus GMTs after vaccination also showed comparable increases in both groups, and showed no significant difference (P = 0.860). In the safety evaluation, solicited local adverse reactions occurred in 81.2% of the subjects in the GC1107 group and in 86.4% of the subjects in the control group. Solicited systemic adverse events occurred in 33.2% of the subjects in the GC1107 group and in 47.2% of the subjects in the control group, which did not reach statistical significance. CONCLUSION: This phase III study demonstrated non-inferiority in immunogenicity and comparable safety of GC1107 compared with the control Td vaccine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02361866
Adult* ; Diphtheria* ; Humans ; Tetanus* ; Vaccination

OBJECTIVE: To investigate the status of vaccination in children with human immunodeficiency virus (HIV) infection. METHODS: A questionnaire survey was performed in 148 children in Hunan province, China who were registered in China's Acquired Immune Deficiency Syndrome Comprehensive Response Information Management System up to December 31, 2016 and were aged <15 years at the time of confirmed diagnosis of HIV infection. The information on vaccination, diagnosis of HIV infection, and diagnosis and treatment of related diseases was collected. RESULTS: Of the 148 children with HIV infection, there were 70 boys (47.3%) and 78 girls (52.7%); 140 children had an age of 3.8 (0.2-14.8) years at the time of confirmed diagnosis, and 8 children refused to answer this question. Mother-to-child transmission was found in 133 children (91.7%), blood transmission in 1 child (0.7%), and unknown in 14 children (9.5%). Of the 148 children, 129 (87.2%) received antiviral therapy and 19 (12.8%) did not receive such treatment. The vaccination rates of hepatitis B vaccine, bacille Calmette-Guérin vaccine, poliomyelitis live attenuated vaccine and diphtheria-pertussis-tetanus vaccine ranged from 70.9% to 77.7%, which was significantly lower than the national level (≥97%); the vaccination rates of the other vaccines in the National Immunization Program gradually decreased with age. No severe adverse effects were reported after vaccination. CONCLUSIONS Mother-to-child transmission is the main route of HIV infection in Chinese children. The diagnosis of children with HIV infection is significantly delayed, with low vaccination rates. Efforts should be made to strengthen early diagnosis, early treatment and vaccination in children with HIV infection, in order to improve their quality of life.
Adolescent ; Child ; Child, Preschool ; China ; Diphtheria-Tetanus-Pertussis Vaccine ; Female ; HIV ; HIV Infections ; Humans ; Infant ; Male ; Quality of Life ; Vaccination

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