关键词： Vaccine(s)   Stability   Analysis   Analytical ultra-centrifugation   Field-flow fractionation (FFF)   Light scattering (static)   Surface plasmon resonance (SPR) spectroscopy  

摘要： Upscaling the production capacity of inactivated poliovirus vaccines (IPV) is urgently needed to eradicate polio worldwide. For the development of a robust manufacturing process for IPV, the impact of stresses on the properties of the poliovirus during manufacturing needs to be carefully evaluated. In this study, the physicochemical properties of Sabin poliovirus after low pH exposure were analyzed by asymmetrical flow field-flow fractionation coupled to multi-angle laser light scattering (AF4-MALS), sedimentation velocity analytical ultracentrifugation (SV-AUC), transmission electron microscopy (TEM), dynamic light scattering (DLS) and surface plasmon resonance (SPR). Low pH stress caused structural changes and aggregation of inactivated poliovirus virions, whereas degraded virion particles would not revert to native virions even after neutralization. Importantly, a complete loss of the D-antigenicity of IPV by low pH stress, followed by neutralization, was observed in SPR. These results suggest that the exposure of poliovirus particle to low pH stress would induce irreversible denaturation and aggregation of virus particles and lead to the loss of D-antigenicity;thus, low pH stress during the manufacturing of poliovirus vaccine should be minimized. The analytical methods above can be efficiently utilized in the development of high-integrity manufacturing processes and high-quality vaccines. (c) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

关键词： Inactivated polio vaccine   Clinical trial   Poliovirus   Sabin strain   Salk strain  

摘要： Background: A domestic Sabin strain-based inactivated poliovirus vaccine (Sabin IPV) was approved by China Food and Drug Administration in 2017 as a replacement for the Salk strain-based inactivated poliovirus vaccine (Salk IPV) that has been in use in China for over 10 years. The present post-marketing trial was implemented in China to assess the immunogenicity and safety of replacing the Salk IPV with the Sabin IPV in the last two immunizations of the standard three-dose schedule. Methods: We conducted a randomized, controlled clinical trial with two groups that received three doses of IPVs at the age of 2, 3, and 4 months: the Salk-Sabin-Sabin group and the Salk-Salk-Salk group. Blood samples were collected before vaccination and 30-40 days after the third dose of vaccination. The seroconversion rates and antibody geometric mean titers (GMTs) were calculated and analyzed to evaluate immunogenicity. The safety of both immunization schedules was also monitored and analyzed. Results: Of 360 recruited healthy infants, all three IPV doses were administered and blood collection was completed in 330 infants. All participants (100%) in both groups were seropositive for all three poliovirus types after the last vaccination. There were significant differences between the two groups (P < 0.001) in the GMTs for antibodies against poliovirus types 1 and 2, but no significant difference was observed for antibodies against type 3 (P = 0.009). A non-inferiority t-test showed that the post-immunization GMTs for all three types in the Salk-Sabin-Sabin group were not inferior to those in the Salk-Salk-Salk group (P < 0.001). Safety assessment indicated that there was no significant difference in the incidence of all adverse events between the two groups (P = 0.806). Conclusions: The Salk-Sabin-Sabin IPV immunization schedule is not inferior to the Salk-Salk-Salk IPV schedule in terms of both immunogenicity and safety. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Movement patterns   Mobile populations   Poliovirus risk   Vaccination   Pakistan and Afghanistan  

摘要： Background: Stopping serotype 1 wild poliovirus transmission in Pakistan and Afghanistan requires ensuring all children <5 years of age are repeatedly vaccinated, including the large proportion living in mobile groups. Vaccinating children living in high-risk mobile populations (HRMPs) remains a priority for the polio programme. Methods: In 2017-2018, group-level censuses were conducted in 43 districts of Pakistan, gathering information for all HRMP children <5 years of age residing in settlements. Demographic and mobility information was collected, including HRMP type, ethnicity, language, mode of transportation and movement patterns. Vaccination status was recorded for the most recent polio campaign. Proportion of HRMP children by demographic factors and mode of transportation was determined and the magnitude of movement was quantified based on the origin, previous and next locations. Magnitude of cross-border movement with Afghanistan was evaluated, as was primary crossing point. Vaccination status was evaluated for each district by demographic and mode of transportation information. Results: In total, 188,130 HRMP children <5 years of age were assessed. The predominant HRMP type, ethnic group, language and mode of transport was Afghan refugees (27%), Pashtun (69%), Pashto (69%) and bus (52%). Overall, 84% of children originated outside of their current district, including 29% from Afghanistan. Previous and next locations, were reported outside of current location by 34% and 77% of children. Afghanistan was previous and next location for 5% and 11% of children, with 5.5% and 3% of children crossing the Afghanistan border in the past 6-months and next 3-months. Primary crossing route was Torkham (79%). Overall vaccination coverage was 98% (IQR: 96%-99%) and consistently >90% across HRMP type, ethnic group, language and mobility means. Conclusion: Large numbers of HRMPs were found across Pakistan, with substantial links throughout the country and with Afghanistan.

关键词： 脊髓灰质炎病毒疫苗,灭活   免疫原性   制备  

摘要： 目的建立Sabin株毒种制备脊髓灰质炎灭活疫苗(inactivated poliovirus vaccine,IPV)生产工艺并评价其免疫原性。方法采用Vero细胞培养Sabin株脊髓灰质炎Ⅰ、Ⅱ、Ⅲ型病毒,制备3价Sabin株IPV(Sabin strain IPV,sIPV)。通过ELISA检测D抗原含量。检测病毒滴度,电子显微镜下观察纯化病毒形态并电泳鉴定,分析抗原纯度,同时检测纯化原液宿主细胞残余DNA和蛋白含量。通过大鼠体内接种法比较sIPV和野生株IPV免疫原性,并观察中和抗体滴度变化。结果Ⅰ、Ⅱ、Ⅲ型收获液D抗原含量分别为2437、365、1253 DU/ml,病毒滴度分别为每毫升8.4、7.8和7.9 lg半数细胞培养物感染量。纯化病毒抗原纯度均>99%。电子显微镜下观察可见直径20~30 nm病毒颗粒,电泳鉴定正确。纯化原液的残余宿主细胞DNA和蛋白含量分别12.3 pg/500μl和9.8 ng/ml。sIPV 3针免疫后在大鼠体内诱导产生抗Ⅰ、Ⅱ、Ⅲ型中和抗体的几何平均滴度分别为9397.8、554.7和4668.4,与野生株IPV相比Ⅰ型明显增高(t=-3.429,P=0.004),Ⅱ、Ⅲ型无明显差别,初免后19周内均维持在较高水平。结论建立了稳定的sIPV生产工艺,制备的sIPV免疫原性较好。

关键词： 急性弛缓性麻痹   脊髓灰质炎病毒   非脊髓灰质炎肠道病毒   血清型  

摘要： 目的分析广东省急性弛缓性麻痹(Acute flaccid paralysis,AFP)病例病原学特征。方法对广东省2015-2017年0-14岁儿童AFP病例粪便标本进行脊髓灰质炎(脊灰)病毒(Poliovirus,PV)和非脊灰肠道病毒(Non-polio enterovirus,NPEV)分离和血清型鉴定,对PV株进行VP1编码区核苷酸序列测定,分析肠道病毒病原谱。结果在2015-2017年1156例AFP病例中,PV、NPEV总阳性率分别为1.90%(22例)、5.97%(69例)。0-4岁儿童病例PV、NPEV阳性率分别为21.10%(22例)、13.29%(59例)。5-7月份病例PV、NPEV阳性率分别为1.86%(6例)、16.15%(52例)。在PV阳性病例中,PV1、PV2、PV3、混合型分别为5例、4例、7例、6例;疫苗类似株、疫苗衍生脊灰病毒分别为21例、1例。结论广东省2015-2017年AFP病例未发现脊灰野病毒;NPEV感染以0-4岁儿童为主且呈夏秋季高峰。

关键词： 脊灰病毒   儿童   检出率   脊灰疫苗  

摘要： 目的了解脊髓灰质炎(脊灰)疫苗转换对福建省儿童脊灰病毒(PV)携带情况的影响。方法采用随机抽样方法,对龙岩、泉州、福州市<6岁儿童进行3次重复横断面调查。结果3次共调查儿童1064例,病毒检出率为21.9%(233例,其中27例为PVⅢ型疫苗相关株、206例为非脊灰病毒);PV检出率以疫苗转换后稳定期最高(3.6%);PV检出率0岁组最高(6.7%);"0"剂次免疫的儿童PV检出率最高(10.0%)、"3"剂次基础免疫的儿童最低(1.7%);3种免疫模式者(减毒、灭活和混合)的PV检出率差异均无统计学意义;27株PVⅢ中,29.6%(8株)在VP1区与Sabin疫苗株完全一致,70.4%(19株)变异位点均<5个,涉及17个位点。结论福建省2016—2019年疫苗转换后儿童PV检出率维持往年水平,均为PVⅢ型疫苗相关株,今后仍需加强脊灰病毒的监测。

关键词： 脊髓灰质炎病毒   AFP病例监测   环境监测  

摘要： 目的评估2016年5月脊灰疫苗免疫策略转换后,泉州市急性弛缓性麻痹病例(AFP)的监测质量,分析外环境污水中脊髓灰质炎病毒(PV)的流行情况,为脊灰防控策略提供依据。方法采用描述性分析方法对2017~2019年泉州市AFP病例个案和外环境监测点采集的污水标本分离结果进行分析。结果 2017~2019年共报告149例AFP病例,平均报告发病率均为3.58/10万,各项监测指标均达到国家方案指标要求。采集148例共296份粪便标本,PV分离率为0.68%(2/296),均为疫苗株,非脊灰肠道病毒(NPEV)分离率为3.38%(10/296)。在13例粪便标本不合格AFP病例的密接者中发现1例Ⅲ型脊灰疫苗衍生病毒(VDPV)携带者,经应急处置后未发生病毒循环。共采集外环境污水标本62份,PV阳性率为27.42%(17/62),均为疫苗株,且以Ⅲ型为优势株,NPEV阳性率为66.13%(41/62)。结论泉州市AFP病例监测质量和敏感度高,发现Ⅲ型VDPV后处置快速科学,成功有效。外环境监测作为脊灰病毒监测的重要补充,能为脊灰流行提供预警。

关键词： 双歧杆菌   二价口服脊髓灰质炎减毒活疫苗   黏膜免疫   免疫球蛋白A  

摘要： 目的探讨双歧杆菌对Ⅰ+Ⅲ型二价脊髓灰质炎(简称脊灰)减毒活疫苗(bivalent oral poliovirus vaccine,bOPV)黏膜免疫的影响。方法给脊灰受体转基因小鼠接种2剂bOPV,间隔28 d,试验组小鼠在每剂bOPV接种前7 d灌胃双歧杆菌,同时对照组小鼠喂PBS。每剂疫苗接种后第3和第7天采集当天小鼠粪便样本,测定其中脊灰特异的IgA水平和排毒水平。在bOPV接种后检测小鼠细胞因子分泌水平和肠道淋巴结的淋巴细胞分群。结果第1剂和第2剂bOPV接种后的第3天,试验组小鼠脊灰特异的黏膜IgA水平均显著高于对照组(P<0.05或<0.01),且第1剂接种第3天,试验组小鼠IgA阳转率显著高于对照组(P<0.05)。试验组小鼠接种第1剂bOPV后第3天,Ⅰ型脊灰病毒排毒量显著低于对照组(P<0.01)。试验组小鼠在bOPV免疫后能激活更多的B淋巴细胞(P<0.000 1)和Th1通路的细胞因子IL-1、TNF-α(P<0.05)。结论双歧杆菌用于bOPV接种前可提高脊灰特异的黏膜免疫IgA分泌水平,且具有一定的减缓排毒作用。

摘要： Background Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV ( f-IPV;a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule. Methods This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks;two f-IPV group);or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks;three f-IPV group);or two doses of intramuscular IPV (administered at 14 and 36 weeks;two IPV group);or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks;three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV;if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three

关键词： 脊髓灰质炎疫苗   疫苗接种   乙肝疫苗   联合疫苗   百日咳   白喉   破伤风   时间延长  

摘要： 谣言1:已经接种过,没有必要进行第2剂次疫苗接种在实际的疫苗接种,过程中,为了延长抗体的存在时间,一般会进行多剂次接种。比如乙肝疫苗、破伤风-白喉-百日咳联合疫苗和脊髓灰质炎疫苗等,至少需要完成3剂次接种才能使身体产生足够的免疫力。此外,随着时间延长,抗体的浓度会逐渐降低,所以有些疫苗还要进行再次接种以加强效果。