关键词： 胶质母细胞瘤   病毒疗法   脊髓灰质炎病毒   CD155   肿瘤细胞   显著延长   细胞裂解   改造后  

摘要： 美国杜克大学研究者发现的突破性病毒疗法,可显著延长胶质母细胞瘤患者生存,可使本来只有4%的3年生存率提高到21%。患者接受经过改造的脊髓灰质炎病毒,（PVSRIPO治疗）这种改造后的病毒可针对表达CD155的肿瘤细胞,选择性地入侵并进行复制,最终使肿瘤细胞裂解。CD155在胶质母细胞瘤中高度表达,研究者期待这一病毒能有效地对其进行攻击。

关键词： 脊髓灰质炎减毒活疫苗   脊髓灰质炎灭活疫苗   序贯免疫   母传抗体  

摘要： 目的探讨婴儿脊髓灰质炎(简称脊灰)母传抗体对Sabin株脊髓灰质炎灭活疫苗(Sabin inactivated poliovirus vaccine,s IPV)与不同剂型脊髓灰质炎减毒活疫苗(oral poliovirus vaccine,OPV)采用不同序贯免疫程序接种效果的影响。方法选取柳州市600名2月龄无脊髓灰质炎疫苗免疫史的常住健康婴儿,分为6个序贯免疫组,其中1剂s IPV+2剂b OPV 2组:s IPV+2b OPV(糖丸)组、s IPV+2b OPV(液体)组;2剂s IPV+1剂b OPV 2组:2s IPV+b OPV(糖丸)组、2s IPV+b OPV(液体)组;2剂s IPV+1剂t OPV 2组:2s IPV+t OPV(糖丸)组,2s IPV+t OPV(液体)组。每组100人。按照0、28、56 d程序,分别在婴儿2、3、4月龄时接种相应疫苗。检测免前、全程免后28 d血清中脊灰中和抗体滴度,计算阳转率及GMT。结果 6个序贯免疫组免前各项指标分布均匀,各型脊灰抗体阳性率、抗体水平及分布均无明显差异。共有518例免前和免后配对血清抗体检测结果的研究对象进入免疫原性分析。s IPV+2b OPV组与2s IPV+b OPV组Ⅱ型抗体、2s IPV+t OPV(糖丸)组Ⅲ型抗体免前阴性和免前阳性者接种疫苗后阳转率差异均有统计学意义;s IPV+2b OPV(糖丸)组Ⅲ型抗体,2s IPV+b OPV(糖丸)组与2s IPV+b OPV(液体)组Ⅱ型抗体,2s IPV+t OPV(糖丸)组Ⅰ、Ⅱ型抗体的免前阳性与免前阴性者接种疫苗后的GMT差异均有统计学意义;2s IPV+t OPV(糖丸)Ⅰ型抗体组与2s IPV+t OPV(液体)Ⅱ型抗体组中,免前8~<32、≥32两种滴度水平的免后GMT差异均有统计学意义。结论脊灰疫苗序贯免疫效果受脊灰母传抗体干扰。

关键词： 脊髓灰质炎病毒疫苗   口服   庆大霉素类   药物残留物   酶联免疫吸附测定   验证  

摘要： 目的验证口服脊髓灰质炎减毒活疫苗（人二倍体细胞）中庆大霉素残留量的检测方法。方法应用庆大霉素ELISA试剂盒建立庆大霉素残留量的检测方法。对该方法标准曲线的线性，线性范围内的准确度、精密度、专属性、耐用性、检测限及定量限进行验证。结果验证的标准曲线线性良好，相关系数〉0．98。该法检测高、中、低浓度的庆大霉素标准品的回收率为92．7％～123．6％；检测同一批次供试品的相对标准偏差为8oA；不同实验人员检测同一批次供试品和不同批次试剂盒检测同一批次供试品，相对标准偏差均〈15％；庆大霉素加样回收率为95．9％～121．3％；该法在（37±1）℃温度范围内耐用性良好；该法测定庆大霉素的检测限为0．040ng／ml，定量限为0．135ng／ml。结论用于检测口服脊髓灰质炎减毒活疫苗（人二倍体细胞）中庆大霉素残留量的方法是有效的。

关键词： ORAL poliomyelitis vaccine   PARALYSIS   POLIOVIRUS   SEROTYPES   DRUG withdrawal symptoms  

摘要： Khalequ Zaman and colleagues provide helpful new information on the performance of serotype 2 monovalent oral poliovirus vaccine (mOPV2).2 This vaccine is held in a stockpile by WHO and released only for response to serotype 2 vaccine-derived poliovirus outbreaks. Since the global withdrawal of serotype 2 oral vaccine, seven circulating serotype 2 vaccine-derived polioviruses have been reported from five countries (as of February, 2018), and all but one appear to have been seeded by trivalent vaccine given before withdrawal.4 Most circulating serotype 2 vaccine-derived polioviruses have required more than two campaigns with mOPV2 because of the challenges in vaccinating children in areas affected by conflict or with poor access to health care. Zaman and colleagues also report no additional benefit when IPV was administered alongside the first dose of mOPV2 at 6 weeks of age.2 The relevance of this finding to outbreak response is less clear because campaigns with IPV are typically used in older children to boost previous immunity induced by oral vaccine.9,10 The additional benefit of IPV will also depend on the immune response induced by oral vaccine alone, which was observed in 157 (91%) of 172 infants after just one dose of mOPV2 in Bangladesh.2 A similar study in Pakistan found that 76% (39 of 51) of seronegative infants aged 6 weeks had an immune response following a single dose of mOPV2, which increased to 100% (15 of 15) when monovalent serotype 2 IPV was co-administered.11 These and other supporting data have motivated IPV use in response to vaccine-derived poliovirus outbreaks despite a shortage of supply.

关键词： poliovirus   vaccine   formulation   stability   delivery   Nanopatch (TM)   microarray patch  

摘要： The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch (TM) (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (similar to 50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained >80% D-antigen potency during drying and subsequent storage for 4 weeks at 4 degrees C, and >60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Pharmacists Association (R).

关键词： Poliovirus   Oral poliovirus vaccine   Vaccine-associated paralytic poliomyelitis   Polio eradication  

摘要： We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an immunocompromised patient with acute lymphocytic leukemia who was initially diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 polio virus from the patient's cerebrospinal fluid made this a case of vaccine-related poliovirus (VRPV) infection. The patient developed paralysis and respiratory distress and deceased a few months after onset of paralysis with respiratory failure. This tragic case report highlights the emergence of VAPP and indicates the importance of timely diagnosis of VRPV infections to improve clinical management of VRPV-infected patients and to prevent the devastating consequences of silent introduction of VRPVs in treatment wards and eventually in the society.

关键词： Poliomyelitis   Vaccine   IPV   L20B cell line   Test for effective inactivation  

摘要： Absence of 'live' residual poliovirus in Inactivated Poliovirus Vaccine (IPV) is routinely checked using Primary Monkey Kidney Cells (PMKC). However, the increasing demand for IPV and the ethical, technical and safety issues associated with the use of non-human primates in research and quality control, has made the replacement of primary cells with an established cell line a priority, in line with the principles of the 3Rs (Replacement, Reduction and Refinement in animal testing). As an alternative to PMKC, we evaluated the L20B cell line;a mouse cell-line genetically engineered to express human poliovirus receptor, CD155. L20B is already used for the detection and diagnosis of poliovirus in clinical samples. We demonstrate the stability of L20B cells in terms of CD155 gene and receptor expression, and permissivity to polioviruses for at least 16 sequential passages. In addition, the L20B cell line was found to be at least as sensitive as PMKC in detecting the presence of 'live' poliovirus in IPV samples. Equivalence or superiority of L20B cells versus PMKCs was demonstrated for assessing the presence of residual 'live' poliovirus in formaldehyde-inactivated preparations for the three poliovirus serotypes. These results demonstrate that the L20B cell line is a suitable alternative to PMKC in IPV inactivation testing.

关键词： VIRUS inactivation   RANDOMIZED controlled trials   IMMUNE response   CELL culture   POLIO vaccination  

摘要： Background Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. Methods We did a randomised, controlled, parallel, open-label,non -inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0.1 mL in total] of about 10550% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0.5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0.05 (one-tailed) was used. This trial is registered at ***, number NCT02643368, and is closed to accrual. Findings Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus I

关键词： 脊髓灰质炎灭活疫苗(Sabin株)   口服脊髓灰质炎减毒活疫苗   贯序接种   抗体滴度   保护率  

摘要： 目的评价我国国产脊髓灰质炎灭活疫苗(Sabin株)和口服脊髓灰质炎减毒活疫苗序贯接种基础免疫的效果。方法采用同期非随机对照实验研究方法,于2015年9~12月期间,在宁夏回族自治区吴忠市同心县选择满2月龄健康儿童180人,按照国家规定的免疫程序,分别在2、3、4月龄各接种1剂次脊髓灰质炎疫苗。将上述儿童分为两组:一组采用t OPV+t OPV+t OPV的基础免疫程序(简称O-O-O组),另一组采用国产IPV(Sabin株)+t OPV+t OPV(简称I-O-O组)序贯接种的基础免疫程序。分别采集同一受种者免疫前和完成3剂次脊髓灰质炎疫苗基础免疫后30 d的血清标本,采用微量中和试验测定血清中3个脊髓灰质炎型别(Ⅰ、Ⅱ、Ⅲ型)的抗体滴度,计算GMT及抗体保护率。结果 3剂次脊髓灰质炎疫苗基础免疫程序接种完成后,I-O-O组脊髓灰质炎Ⅱ、Ⅲ型抗体滴度均高于O-O-O组;两组均获得较好的针对3种型别脊髓灰质炎病毒的抗体保护率,差异无统计学意义(P>0.05)。结论国产IPV(Sabin株)和t OPV序贯接种的免疫程序能够提供与全程接种t OPV相似甚至更高的针对脊髓灰质炎病毒的免疫保护能力。

关键词： 疑似预防接种异常反应   监测   脊髓灰质炎减毒活疫苗   脊髓灰质炎灭活疫苗  

摘要： 目的比较分析2015—2017年湖北省脊髓灰质炎(脊灰)疫苗接种后疑似预防接种异常反应(AEFI)的发生特征,评价脊灰疫苗安全性。方法采用描述流行病学方法对湖北省2015—2017年AEFI信息管理系统三价脊灰减毒活疫苗(Tt OPV)、Salk株脊灰灭活疫苗(IPV-Salk)、Sabin株脊灰灭活疫苗(IPV-Sabin)、二价脊灰减毒活疫苗(b OPV)AEFI个案数据进行统计分析。结果湖北省2015—2017年t OPV、b OPV、IPV-Salk、IPV-Sabin接种后AEFI报告发生率4.78/10万剂~26.94/10万剂。4种脊灰疫苗接种后AEFI中,一般反应均占80%以上,异常反应占11.6%~20.56%,男童均多于女童,发生年龄均以<1岁组为主,90%以上AEFI发生在接种后≤1 d。脊灰减毒活疫苗第1剂次AEFI发生率明显高于后续剂次,脊灰灭活疫苗各接种剂次间AEFI发生率无差异。新上市的b OPV和IPV-Sabin AEFI发生率分别高于t OPV和IPV-Salk,但多以一般反应和过敏性皮疹为主。结论湖北省脊灰疫苗安全性良好,但仍需关注罕见异常反应病例的发生。