关键词： Silk   Fibroin   Stabilization   Vaccine   Poliovirus  

摘要： Current inactivated polio vaccine (IPV) products are sensitive to both freezing and elevated temperatures and therefore must be shipped and stored between 2 degrees C and 8 degrees C, a requirement that imposes financial and logistical challenges for global distribution. As such, there is a critical need for a robust, thermally stable IPV to support global polio eradication and post-eradication immunization needs. Here, we present the development of air-dried thin films for temperature stabilization of IPV using the biomaterial silk fibroin. Thin-film product compositions were optimized for physical properties as well as poliovirus Dantigen recovery and were tested under accelerated and real-time stability storage conditions. Silk fibroin IPV films maintained 70% D-antigen potency after storage for nearly three years at room temperature, and greater than 50% potency for IPV-2 and IPV-3 serotypes at 45 degrees C for one year. The immunogenicity of silk fibroin IPV films after 2-week storage at 45 degrees C was assessed in Wistar rats and the stressed films generated equivalent neutralizing antibody responses to commercial vaccine for IPV-1 and IPV-2. However, the absence of IPV-3 responses warrants further investigation into the specificity of ELISA for intact IPV-3 D-antigen. By demonstrating immunogenicity post-storage, we offer the air-dried silk film format as a means to increase IPV vaccine access through innovative delivery systems such as microneedles. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： 无细胞百白破-Sabin株脊髓灰质炎联合疫苗   免疫   感染   保护效果  

摘要： 目的观察候选无细胞百白破-Sabin株灭活脊髓灰质炎联合疫苗(DTaP-sIPV)在大鼠中的免疫保护效果,为疫苗临床前研究提供依据。方法将候选疫苗DTaP-sIPV、无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗(DTaP-IPV/Hib)、吸附无细胞百白破-b型流感嗜血杆菌联合疫苗(DTaP/Hib)、百日咳疫苗效力参考品(全细胞疫苗,wP)按0、30、60 d 3剂免疫程序免疫Wistar大鼠,检测各组大鼠每剂免疫后的血清中各组分抗体水平。在免疫完成后3周,用百日咳18323株通过气雾攻击的方式感染大鼠。在感染后的第3、7、14、21和28天检测各组白细胞数、肺部菌落克隆形成数以及百日咳疫苗组分抗体变化水平。结果候选疫苗组3剂次免疫完成后PT抗体几何平均滴度(GMT,log2)为16.74,FHA抗体GMT为18.44,PRN抗体GMT为10.75,DT抗体GMT为17.34,TT抗体GMT为17.84,针对3种Sabin脊髓灰质炎病毒株(Ⅰ、Ⅱ和Ⅲ型)的抗体的GMT分别为7.57、8.41和9.70,均达到100%阳转。候选疫苗抗原组分抗体除了PRN和I型IPV外,其他组分抗体水平均与疫苗对照组相比无显著性差异。在基础免疫完成后3周对大鼠进行百日咳杆菌气雾攻击,各疫苗组均表现较好的保护效果,白细胞水平都呈现平稳状态,虽然在肺部也检测到少量细菌定植,但各疫苗组间差异不明显,且在感染后第28天都清除至检测限;而空白对照组在肺部则检测到了大量细菌定植,且在感染后第28天都并未清除至检测限,百日咳特异性的FHA和PRN抗体在感染后的第14天也出现了相应的升高。结论候选疫苗在Wistar大鼠模型上具有较好的免疫保护效果。

关键词： 脊髓灰质炎疫苗   北京协和医学院   顾方舟   中国医学科学院   人的生命   浙江宁波   无脊髓灰质炎   科技攻关  

摘要： 顾方舟是我国病毒学家,脊髓灰质炎疫苗研发生产的拓荒者、科技攻关的先驱者,为实现我国全面消灭脊髓灰质炎奉献了一生。他研发的脊髓灰质炎疫苗“糖丸”,护佑了几代中国人的生命健康,使中国进入无脊髓灰质炎时代。顾方舟,1926年6月生,浙江宁波人,中国医学科学院北京协和医学院原院校长、研究员。1955年,江苏南通暴发大规模的脊髓灰质炎疫情,随后疫情迅速蔓延。顾方舟临危受命,开始了脊髓灰质炎疫苗的研究工作。

关键词： 脊髓灰质炎   脊髓灰质炎病毒   消灭   封存   泄露   认证  

摘要： 在消灭特定型别野生脊髓灰质炎(脊灰)病毒后,源自保存脊灰病毒设施泄漏的病毒,会增加已经消灭病毒在人群中重新传播的风险。中国目前尚未制定封存脊灰病毒的完整方案,封存工作的进展滞后于全球的要求。为了在中国最大程度地降低脊灰病毒泄露的风险,相关权威机构需要依据国家法规和部门规章,登记清册脊灰病毒并评价工作质量,建立机制,定期更新持有Sabin株脊灰病毒或潜在感染性材料清单;销毁非必需设施保存的Ⅱ型Sabin株脊灰病毒和潜在感染性材料;重点关注必需设施持有的脊灰病毒,建立国家脊灰病毒封存监管机构认证的必需设施。

关键词： 脊髓灰质炎疫苗低变异株病毒   监测   诊断   处理  

摘要： 讨论脊髓灰质炎疫苗低变异株病毒病例的监测、诊断、处理方法与预防脊髓灰质炎疫苗低变异株病毒病例发生的策略。根据此病例的个案调查、预防接种相关信息、临床诊断、治疗与脊髓灰质炎实验室病毒检测等方面的资料进行分析。脊髓灰质炎疫苗低变异株病毒病例监测、诊断、处理仍需改进,须严格把握Ⅰ+Ⅲ型脊髓灰质炎减毒活疫苗接种禁忌证,进一步改进消灭脊髓灰质炎免疫策略,预防脊髓灰质炎疫苗低变异株病毒病例的发生。

关键词： 脊髓灰质炎   免疫成功率   抗体水平   监测  

摘要： 目的了解北京市顺义区脊髓灰质炎疫苗基础成功率和抗体水平。方法采用随机抽样的方法抽取3个乡镇街道作为调查点,选择符合条件的47例儿童,采用微量中和实验法测定脊髓灰质炎中和抗体,中和抗体≥1∶4判断阳性。结果47例儿童的脊灰Ⅰ型、Ⅲ型抗体阳性率均为100%,脊灰病毒中和抗体平均滴度分别为Ⅰ型1∶512(1∶512~1∶1024)、Ⅲ型1∶512(1∶512~1∶1024)。Ⅰ型和Ⅲ型脊灰病毒中和抗体分布差异无统计学意义(P>0.05),不同调查点、男女和是否及时接种的Ⅰ型、Ⅲ型脊灰病毒中和抗体平均滴度的分布差异无统计学意义(P>0.05)。结论引入bOPV后IPV-b OPV序贯免疫程序的基础免疫效果良好。

关键词： 色谱法,离子交换   脊髓灰质炎病毒疫苗,灭活   阴离子交换树脂类  

摘要： 目的研究Sabin株脊髓灰质炎病毒(Sabin strain polio virus,sPV)纯化的离子交换层析(ion exchange chromatography,IEC)条件。方法在不同层析条件下对sPV凝胶层析粗纯液进行IEC,设定的层析参数分别为介质Q Sepharose FF或Eshmuno Q、上样量30%或40%柱体积、流速(150±5)或(240±8)cm/h。分别检测各型sPV纯化液的D抗原含量、蛋白浓度、病毒滴度、宿主细胞蛋白残留量和Vero细胞DNA残留量,计算D抗原回收率和比活。结果Eshmuno Q IEC纯化的各型sPV纯化液的D抗原回收率均明显高于Q Sepharose FF IEC。在上样量40%柱体积、流速(150±5)cm/h条件下,Eshmuno Q IEC纯化的各型sPV纯化液的D抗原比活均高于Q Sepharose FF IEC,差异均有统计学意义(Ⅰ型:t=4.23,Ⅱ型:t=5.73,Ⅲ型:t=4.18,P值均<0.05),而且前者的宿主细胞蛋白残留量(Ⅰ型:t=8.29,Ⅱ型:t=7.89,Ⅲ型:t=8.18,P值均<0.05)和Vero细胞DNA残留量(Ⅰ型:t=4.23,Ⅱ型:t=4.56,Ⅲ型:t=4.78,P值均<0.05)均低于后者,差异均有统计学意义。结论用IEC纯化sPV时,以Eshmuno Q代替Q Sepharose FF可增加上样量和流速,从而缩短IEC时间,提高纯化效率。

关键词： 脊髓灰质炎病毒   全球监测   基因学   免疫学   野生型   全球范围   病毒学   尼日利亚  

摘要： 继野生型脊髓灰质炎病毒2型(WPV2)之后,WPV3也已在全球范围被消灭,全球监测到的最后1例WPV3感染病例于2012年发生在尼日利亚。脊髓灰质炎病毒包含3个免疫学特异的野生型:WPV1、WPV2和WPV3,虽然感染后症状完全相同,但各型间存在基因学和病毒学差异。

摘要： Poliomyelitis, also known as polio, is a highly infectious viral disease, predominantly affecting children under five years old. The virus is transmitted from person-to-person and mainly spreads through the fecal-oral route. The virus multiplies in the intestine, from where it can invade the nervous system via the bloodstream, potentially causing paralysis. Polio symptoms include fever, fatigue, headache, vomiting, neck stiffness and pain in the limbs. The disease causes permanent paralysis in one out of 200 infections. Currently, there is no cure for polio; it can only be prevented by immunisation.1

关键词： Bladder cancer   CD155   Prognosis   Adjuvant Chemotherapy  

摘要： Objective: To investigate the expression pattern of CD155 and evaluate the prognostic value of CD155 in muscle-invasive bladder cancer (MIBC). Patients and methods: Immunohistochemical staining of CD155 and survival analysis were conducted on 228 nonmetastatic MIBC patients underwent radical cystectomy in cohorts from Fudan University Shanghai Cancer Center and Zhongshan Hospital. Association of CD155 gene expression with tumor stage and survival were analyzed in TCGA and GSE13507 dataset. Results: CD155 was significantly up-regulated in MIBC compared to matched normal urothelium and majorly stained on the membrane of tumor cells. In Fudan MIBC cohort, CD155 high expression was significantly correlated with shorter recurrence-free survival (HR = 2.13, P < 0.001) and overall survival (HR = 2.49, P < 0.001). CD155 expression, T stage, and lymph node status were independent factors for predicting survival in multivariate analysis. In TCGA dataset, CD155 high expression was independently associated with shorter overall survival (HR = 1.74, P = 0.001) beyond age, T stage, and lymph node status. Further, explorative analysis in Fudan MIBC cohort showed that adjuvant chemotherapy was associated with longer recurrence-free survival and overall survival in stage III and IV disease with CD155-high tumors. Conclusions: These findings suggest that CD155 is a robust prognostic factor and may help predict the benefit of adjuvant chemotherapy in MIBC. (C) 2019 Elsevier Inc. All rights reserved.