diphtheria

白喉
  • 文章类型: Journal Article
    2018年在广州进行了血清流行病学研究,以评估白喉和破伤风抗体。中国。用酶联免疫吸附测定法测量白喉和破伤风抗体浓度。总共715名受试者被纳入研究。总体白喉和破伤风类毒素IgG特异性抗体水平为0.126IU/mL(95%CI:0.115,0.137)和0.210IU/mL(95%CI:0.185,0.240),总体阳性率分别为61.82%(95%CI:58.14,65.39)和71.61%(95%CI:68.3,74.92),分别。白喉和破伤风抗体浓度随年龄而降低,随剂量而增加。白喉和破伤风抗体的几何平均浓度和阳性率最低,低于14岁以上人群的基本保护水平。与儿童和青少年相比,中年人和老年人感染白喉棒状杆菌和破伤风梭菌的风险要高得多。目前的白喉和破伤风免疫接种计划不能在儿童期后提供持续的保护。迫切需要调整现行的免疫计划。
    A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were measured with an enzyme-linked immunosorbent assay. A total of 715 subjects were enrolled in the study. The overall diphtheria and tetanus toxoid IgG-specific antibody levels were 0.126 IU/mL (95% CI: 0.115, 0.137) and 0.210 IU/mL (95% CI: 0.185, 0.240), respectively; the overall positivity rate was 61.82% (95% CI: 58.14, 65.39) and 71.61% (95% CI: 68.3, 74.92), respectively. The diphtheria and tetanus antibody concentration was decreased by age and increased by doses. The geometric mean concentrations and positivity rate of diphtheria and tetanus antibodies were lowest and below the essential protection level in people over 14 years of age. Compared to children and adolescents, middle-aged people and the aged are at much higher risk of infection with Corynebacterium diphtheriae and Clostridium tetani. The current diphtheria and tetanus immunization schedule does not provide persistent protection after childhood. There is an urgent need to adjust the current immunization schedule.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    亚太国家在健康和经济条件上高度不同,可能会影响疫苗的获取和使用。我们的研究旨在使用IQVIA-MIDAS数据库描述2019年至2022年10个国家/地区基于DTP的联合疫苗的健康获取模式。可用性,负担能力,使用Spearman的等级相关系数,通过国家健康和经济绩效指标比较了各国的可及性。我们的研究结果表明,在亚太地区,获得基于DTP的疫苗的三个方面差异很大,在健康和经济表现更好的国家,水平更高。受COVID-19大流行的影响,在低收入国家,疫苗的可获得性波动很大,2019年至2021年,菲律宾和印度尼西亚的DTP覆盖率下降了14%以上。对于可用性和可负担性,来自高收入群体的新加坡和马来西亚受到很大影响,这可能与卫生支出占国内生产总值的百分比有关(系数=0.39,p=0.03)。我们的研究表明,需要更多地关注国家卫生支出和常规免疫服务,以改善疫苗差距,并在突发公共卫生事件期间提高疫苗供应链的稳健性和韧性。
    The Asia-Pacific countries are highly diverse in health and economic conditions that may impact vaccine access and uptake. Our study aimed to characterize patterns of health access to DTP-based combination vaccines in 10 countries from 2019 to 2022 using the IQVIA-MIDAS database. The availability, affordability, and accessibility were compared across countries by national health and economic performance indicators using Spearman\'s rank correlation coefficient. Our findings showed that the three aspects of access to DTP-based vaccines varied substantially in the Asia-Pacific region, with higher levels in countries with better health and economic performance. Affected by the COVID-19 pandemic, vaccine accessibility fluctuates significantly in lower-income countries, with DTP coverage rates falling by more than 14% in the Philippines and Indonesia between 2019 and 2021. For availability and affordability, Singapore and Malaysia from high-income groups were largely affected, which may be related to health expenditure as a percentage of gross domestic product (Coefficient = 0.39, p = 0.03). Our study indicates that greater attention needs to be paid to national health expenditure and routine immunization services to improve vaccine disparities and increase the robustness and resilience of the vaccine supply chain during public health emergencies.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Systematic Review
    一名20个月大的女孩因进行性肌肉无力被诊断为格林-巴利综合征(GBS),无反射,和脑脊液的白蛋白细胞解离。尽管及时和系统的治疗,她最终瘫痪了。女孩的GBS和DTaP疫苗接种之间存在时间相关性,但是两者之间的确切因果关系仍然存在争议。此外,我们通过系统评价,总结了其他45例发表的DTP疫苗(或含破伤风的疫苗物质)后GBS病例的临床特征.平均发病年龄,性别分布,接种疫苗后的发病时间,检测抗神经节苷脂抗体,并分析了DTP疫苗(或含破伤风的疫苗物质)接种后GBS的其他基本临床特征。疫苗接种后GBS的时间模式与感染后GBS的时间模式相似。在这里,我们报告了这种罕见的DTaP疫苗接种后推定儿科GBS病例,并回顾了类似病例,以提请医务人员注意疫苗接种后的类似事件.已经提出了DTP疫苗和GBS之间的关联,这两个事件之间的因果关系值得进一步探讨。此外,强烈建议在接种疫苗后对GBS进行监测和警惕.
    A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl\'s GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    针对重要疾病的广泛接种疫苗对全球卫生安全起着关键作用。特别是在COVID-19大流行的背景下。然而,由于对疫苗质量和安全性的怀疑,建立和保持对免疫服务的信任仍然面临挑战。中国定期面临越来越大的压力,甚至是由劣质疫苗事件引发的公众愤怒。我们的目的是评估白喉的影响,百日咳,和2018年中国破伤风(DPT)疫苗丑闻以及随之而来的疫苗接种错误信息,并调查种族和社会经济因素对丑闻的不同反应。根据四川省2017年1月至2018年12月的数据,中国,我们使用差异(DID)方法来比较县级每月DPT疫苗接种与乙型肝炎疫苗接种的变化,在DPT疫苗丑闻之前和之后。我们发现,由于疫苗丑闻和随之而来的错误信息,DPT疫苗接种数量减少了14.0%。少数民族地区接种疫苗的数量,欠发达地区,医疗资源匮乏的地区比非少数民族地区减少更多,发达地区,以及医疗资源良好的地区(24.5%对10.1%,17.3对8.3%,17.0对8.7%,分别)。丑闻发生后,人们在网上搜索了更多的“不合格疫苗”和“百白破疫苗”,与社会经济弱势群体相比,社会经济弱势群体的搜索更多。结果表明,迫切需要通过互联网轻松获取有关疫苗的真实信息,特别是社会经济弱势群体。我们对中国的发现也可以对其他国家更好地维护公共卫生的免疫服务规划产生影响。特别是发展中的。
    Widespread vaccination against important diseases plays a key role for global health security, particularly in the context of the COVID-19 pandemic. However, building and maintaining trust in immunization services remains challenging because of doubts about quality and safety of vaccines. China has periodically faced mounting pressure and even public outrage triggered by incidents of poor-quality vaccines. We aimed to evaluate the impact of the diphtheria, pertussis, and tetanus (DPT) vaccine scandal of 2018 in China and the ensuing misinformation on vaccination, and investigate differential responses to the scandal by ethnic and socioeconomic factors. With data from January 2017 to December 2018 in Sichuan province, China, we used a difference-in-differences (DID) method to compare the changes in the county-level monthly DPT vaccinations against the hepatitis B vaccinations, both before and after the DPT vaccine scandal. We found that the number of DPT vaccinations decreased by 14.0 percent in response to the vaccine scandal and ensuing misinformation. The number of vaccinations in minority regions, under-developed regions, and regions with poor medical resources decreased more than in non-minority regions, developed regions, and regions with good medical resources (24.5 versus 10.1 percent, 17.3 versus 8.3 percent, and 17.0 versus 8.7 percent, respectively). People did more online searching for \"Substandard vaccine\" and \"DPT vaccine\" after the scandal, with the socioeconomically advantaged group searching more compared with the socioeconomically disadvantaged group. The results suggest the urgent need to make true information about the vaccine easily accessible over the internet, especially for the socioeconomically disadvantaged groups. Our findings for China can also have implications for immunization service planning for better safeguarding public health in other countries, particularly developing ones.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    疫苗接种后的安全性是主要的公共卫生问题。尚未明确确定免疫反应的遗传易感性。阐明个体遗传易感性是否在不良事件(AE)中起作用对于预防AE至关重要。
    从2019年7月到2020年6月,我们在中国七个省份的3-24个月儿童中进行了病例对照研究。每个孩子都接受了白喉联合疫苗接种,破伤风,无细胞百日咳,和b型流感嗜血杆菌(DTaP-Hib)。通过每日电话随访,我们在7天内收集了AE。收集口腔拭子样品以研究单核苷酸多态性(SNP)对AE风险的影响。
    304名参与者被纳入研究。在单变量分析中,我们发现了三个保护性SNP(rs452204,OR=0.67,P=0.0352;rs9282763和rs839,OR=0.64,P=0.0256)和一个风险SNP(rs9610,OR=2.20,P=0.0397)。在多变量分析中,发现rs452204和rs839的作用是稳定的。rs452204和rs9610之间存在相互作用(OR=7.25,95%CI:1.44-36.58,P=0.0165)。
    遗传易感性与DTaP-Hib疫苗接种后的AE风险相关,强调在预防AE中的潜在应用。
    Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs.
    From July 2019 to June 2020, we performed a case-control study among children aged 3-24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs.
    304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44-36.58, P = 0.0165).
    Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:本研究旨在评估白喉对健康和经济的影响,破伤风,全细胞百日咳疫苗(DTwP)和白喉-破伤风-无细胞百日咳疫苗(DTaP)疫苗接种对我国百日咳防治的作用.
    方法:我们使用决策树模型进行了成本效益分析,其中包含1978年之前和1978年至2017年期间的历史疫苗接种覆盖率水平以及百日咳发病率和死亡率数据。我们对从出生到死亡的40个出生队列进行了建模。从直接成本和社会角度(直接和间接成本)估计成本和收益。成本和收益调整为2017年美元(USD),未来价值以3%的年利率贴现。我们计算了5岁以下儿童百日咳疫苗接种的净收益值(净储蓄)和收益成本比。我们通过在合理的范围内改变关键参数进行了敏感性分析。
    结果:未接种DTwP和DTaP疫苗,在40个队列中,估计有1.15.76亿例百日咳病例和426650例百日咳死亡.使用DTwP/DTaP疫苗接种,百日咳病例和死亡人数分别下降了92.57%和97.43%,从社会角度来看,节省了46987.81万美元的直接成本和82013.37万美元。从直接成本和社会角度来看,百日咳疫苗接种计划的费用分别为216876万美元和396128万美元。从直接成本的角度来看,效益成本比为21.67:1,从社会角度来看为20.70:1。敏感性分析显示结果是稳健的。
    结论:在40个出生队列的一生中,中国的免疫计划是防止93%的百日咳病例和97%的百日咳死亡,从而为医疗保健系统和社会节省了大量资金。
    This study aimed to evaluate the health and economic impact of diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) and diphtheria-tetanus-acellular pertussis vaccine (DTaP) vaccination on pertussis prevention and control in China during the 40 years from 1978 to 2017.
    We conducted cost-benefit analyses with a decision tree model populated with historical vaccination coverage levels and pertussis incidence and mortality data from before 1978 and during 1978 to 2017. We modeled 40 birth cohorts from birth until death. Costs and benefits were estimated from direct cost and societal perspectives (direct and indirect costs). Costs and benefits were adjusted to 2017 US dollars (USD), and future values were discounted at a 3% annual rate. We calculated net benefit values (net savings) and benefit-cost ratios of pertussis vaccination of children younger than 5 years. We conducted sensitivity analyses by varying key parameters within plausible ranges.
    Without DTwP and DTaP vaccination, there would be an estimated 115.76 million pertussis cases and 426 650 pertussis deaths in the 40 cohorts. With DTwP/DTaP vaccination, pertussis cases and deaths were decreased by an estimated 92.57% and 97.43%, saving 46 987.81 million USD in direct costs and 82 013.37 million USD from societal perspective. Pertussis vaccination program costs were 2168.76 million USD and 3961.28 million USD from direct cost and societal perspectives. Benefit-cost ratios were 21.67:1 from the direct cost perspective and 20.70:1 from the societal perspective. Sensitivity analyses showed the results to be robust.
    Over the lifetime of 40 birth cohorts, China\'s immunization program is preventing 93% of pertussis cases and 97% of pertussis deaths, resulting in substantial savings to the healthcare system and society.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    通过检测陕西省成人百日咳和白喉抗体水平,确定成人百日咳的估计发病率和是否需要加强剂量。中国。2017年采集陕西省18-59岁健康人群的血液样本。血清免疫球蛋白G(IgG)抗体的百日咳毒素(PT)和白喉毒素(DT)使用酶联免疫吸附试验测定。从中国疾病预防控制信息系统收集陕西省百日咳报告病例数据,并与本研究结果进行比较。共纳入4307名受试者。抗PTIgG的平均浓度为19.6IU/mL(95%CI=18.9-20.3),阳性率(≥40IU/mL)为11.0%(474/4307),其中近期感染(≥100IU/mL)占1.2%(53/4307)。2017年仅报告了一例成人百日咳病例,远低于本研究的结果。抗DTIgG的平均浓度为0.04IU/mL(95%CI=0.04-0.05),阳性率(≥0.01IU/mL)为82.3%(3543/4307)。抗DTIgG的平均浓度从18-29岁组的0.07IU/mL下降到50-59岁组的0.03IU/mL,阳性率从86.7%下降到78.7%。我们的研究表明,百日咳在成年人中并不少见。现有的监测系统可能低估了百日咳的真实发病率。白喉抗体水平随年龄增长而降低。青少年和年轻人应考虑接种百日咳疫苗。
    To determine the estimated pertussis incidence in adults and the need for a booster dose by detecting pertussis and diphtheria antibody levels in adults in Shaanxi province, China. Blood samples were collected from healthy individuals aged 18-59 years in Shaanxi province in 2017. Serum immunoglobulin G (IgG) antibodies against pertussis toxin (PT) and diphtheria toxin (DT) were determined using enzyme-linked immunosorbent assay. The data on reported pertussis cases in Shaanxi province were collected from the China Information System for Disease Control and Prevention and compared with the results of this study. A total of 4307 subjects were enrolled. The mean concentration of anti-PT IgG was 19.6 IU/mL (95% CI = 18.9-20.3), and the positive rate (≥40 IU/mL) was 11.0% (474/4307), of which recent infections (≥100 IU/mL) accounted for 1.2% (53/4307). Only one adult case of pertussis was reported in 2017, which is much lower than the results of this study. The mean concentration of anti-DT IgG was 0.04 IU/mL (95% CI = 0.04-0.05), and the positive rate (≥0.01 IU/mL) was 82.3% (3543/4307). The mean concentration of anti-DT IgG decreased from 0.07 IU/mL in the 18-29 year-old group to 0.03 IU/mL in the 50-59 year-old-group, and the positivity rate decreased from 86.7% to 78.7%. Our study suggests that pertussis is not uncommon among adults. The existing surveillance system might have underestimated the true incidence of pertussis. The diphtheria antibody levels decreased with age. Booster vaccination against pertussis should be considered for adolescents and young adults.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    考虑到在中国接种sIPV和DTaP疫苗在3个月和4个月的年龄重叠,减轻父母的治疗负担,提高疫苗接种率,我们设计了一项联合用药的上市后临床研究。
    基于萨宾毒株的灭活脊髓灰质炎病毒疫苗(sIPV)和白喉-破伤风-无细胞百日咳疫苗(DTaP)已在中国获得许可多年。对与DTaP同时施用时sIPV的安全性和免疫原性进行临床研究。
    研究人群分为三组:第1组是sIPV+DTaP伴随给药组,第2组为SIPV接种组,第3组为DTaP接种组。在接种前和接种后30天收集血样,检测血清抗体水平。
    本研究显示,1组1、2、3型脊髓灰质炎病毒的血清阳性率和血清转换率均高于2组,接种后差异无统计学意义(P>0.05)。第1组和第3组除了抗FHA外,对所有疫苗抗原也显示出相似的反应(97.65(94.09-99.36)与100(97.89-100))。各组间DTaP和sIPV的几何平均滴度(GMT)具有可比性,非劣效性t检验结果为P<0.001。第1组报告的局部不良事件(AEs)数量(29.91%)高于第2组(12.39%)和第3组(21.93%)。其中最常见的是发红。同样,最常见的全身性AE是发热.专家确定所有5例严重AE(SAE)病例与研究期间的疫苗无关。
    DTaP和sIPV共同给药的血清转化和安全性相似的证据支持共同给药支持在常规婴儿免疫中引入同时给药两种疫苗的策略。它可以增加疫苗接种覆盖率,保护更多的婴儿免受这些相关疾病的发病率和死亡率。
    https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1,标识符NCT04054882。
    UNASSIGNED: Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration.
    UNASSIGNED: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP.
    UNASSIGNED: The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected.
    UNASSIGNED: This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study.
    UNASSIGNED: The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases.
    UNASSIGNED: https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    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 NCTC11397T (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.
    为探讨糖尿病患者足趾感染的病因,采用微生物形态学结合分子生物学方法对2021年9月海南省人民医院的1例老年糖尿病患者足趾伤口分泌物培养分离出的白喉棒状杆菌溯源分析,为临床感染诊断提供参考。通过革兰染色、Albert法染色镜检、VITEK 2 Compat鉴定仪和MALDI-TOF MS质谱仪鉴定结合16S rRNA基因序列溯源分析,同时开展tox毒力基因检测。结果显示分离菌株镜检为革兰阳性杆菌,有异染颗粒,可发酵大多数糖类,符合白喉棒状杆菌生物学特性;16S rRNA序列与白喉棒状杆菌标准菌株Corynebacterium diphtheriae NCTC 11397T(GenBank登记号:MW682323.1)同源性为100%;tox毒力基因阴性。本研究结果为临床微生物实验室准确鉴定非产毒白喉棒状杆菌奠定了基础,同时为临床认识非产毒白喉棒状杆菌的感染风险提供依据。.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    甲醛解毒是将破伤风毒素(TT)和白喉毒素(DT)转化为破伤风类毒素(TTd)和白喉类毒素(DTd)的过程,分别。这种解毒过程的机制已经通过先前的基于实验室规模类毒素的若干研究进行了研究。为了更好地了解甲醛引起的影响,在这项工作中,研究了从不同脱毒过程中获得的工业TTd和DTd批次。使用液相色谱-质谱(LC-MS),确定了TTd和DTd的15和20个可重复的甲醛诱导修饰位点,分别。通过LC-MS观察到具有较高甲醛诱导修饰率的类毒素,在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)上也有较大的条带。通过SDS-PAGE和LC-MS确认在尺寸排阻色谱(SEC)上观察到的聚集体。甲醛解毒还导致等电点(pI)值降低,并增加在弱阴离子交换(WAX)柱上的保留。进行特定毒性测试以评估在不同解毒条件下获得的TTd和DTd样品的毒性。特定毒性试验的结果表明,本研究中使用的所有类毒素均合格,包括从温和和剧烈的解毒条件下获得的类毒素。然而,与从剧烈的解毒条件获得的疫苗相比,从轻度解毒条件获得的疫苗具有更少的聚集体,并且可能导致缀合疫苗中的糖基化程度更高。因此,我们建议应使用温和的解毒条件来获得TTd和DTd。此外,以及研究甲醛在TTd和DTd中引起的修饰和毒性,还研究了解毒过程对外源蛋白的影响。与类毒素的单体相比,聚集体中观察到外源蛋白的增加。此外,由于交联的形成,毒素单体中的一些外源蛋白质转移到类毒素的聚集体中。为了消除疫苗接种计划中外来蛋白与类毒素交联的风险,在解毒过程和/或在疫苗中使用类毒素之前,纯化过程是必要的。
    Formaldehyde detoxification is a process for converting tetanus toxin (TT) and diphtheria toxin (DT) into tetanus toxoid (TTd) and diphtheria toxoid (DTd), respectively. The mechanism of this detoxification process has been investigated by several previous studies based on lab-scale toxoids. To obtain greater insights of the effects induced by formaldehyde, industrial TTd and DTd batches obtained from different detoxification processes were studied in this work. Using liquid chromatography-mass spectrometry (LC-MS), 15 and 20 repeatable formaldehyde-induced modification sites of TTd and DTd were identified, respectively. Toxoid which had a higher formaldehyde-induced modification rate observed by LC-MS, also had larger bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aggregates which were observed on size exclusion chromatogram (SEC) were confirmed by SDS-PAGE and LC-MS. Formaldehyde detoxification also led to a decrease of isoelectric point (pI) values and an increase of retention on weak anion exchange (WAX) column. Specific toxicity tests were conducted to evaluate toxicity of the TTd and DTd samples obtained with different detoxification conditions. Results from the specific toxicity tests showed that all toxoids used in this study were qualified, including toxoids obtained from mild and drastic detoxification conditions. However, obtained from mild detoxification conditions had less aggregates and may lead to a higher degree of glycosylation in conjugate vaccines than the ones obtained from drastic detoxification conditions. Thus, we suggest that mild detoxification conditions should be used to obtain TTd and DTd. Furthermore, as well as studying the formaldehyde-induced modifications and toxicity in TTd and DTd, the effects of the detoxification process on foreign proteins were also investigated. An increase in foreign proteins were observed in the aggregate than in the monomer of the toxoids. Additionally, some foreign proteins in the monomer of the toxins transferred to the aggregate of toxoids due to the formation of cross-linking. To eliminate the risk of cross-linking foreign proteins to toxoids in vaccination programs, a purification process is necessary before the detoxification process and/or the use of toxoids in vaccines.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号