关键词： 脊髓灰质炎   脊髓灰质炎病毒疫苗   免疫原性   安全性  

摘要： 目的比较Sabin株脊髓灰质炎灭活疫苗(sIPV)与Ⅰ+Ⅲ型脊髓灰质炎减毒活疫苗(人二倍体细胞)(bOPV)液体剂型作为基础免疫以不同接种序贯接种于≥2月龄婴儿中的免疫原性和安全性。方法2017—2018年,采用随机、盲法、单中心、平行对照设计,选择杭州市≥2月龄的婴儿为研究对象,将其分为1sIPV+2bOPV组、2sIPV+1bOPV组和3sIPV组,按照2、3、4月龄的免疫程序,共接种3剂。记录受试者接种后发生的不良反应事件;全程免疫后28~35 d,采集排除脱落者和违背试验方案者血样,采用细胞培养微量中和试验测定抗脊髓灰质炎病毒Ⅰ、Ⅱ、Ⅲ型中和抗体几何平均滴度(GMT),计算抗体阳转率,并对其进行统计学分析。结果1sIPV+2bOPV组、2sIPV+1bOPV组和3sIPV组全部不良反应发生率分别为3.57%、3.61%和1.19%(χ^2=1.190,P=0.552),均为一般反应。全程免疫后,1sIPV+2bOPV组、2sIPV+1bOPV组和3sIPV组Ⅰ型脊髓灰质炎病毒抗体阳转率分别为100%(84/84)、100%(83/83)和100%(84/84),Ⅱ型分别为81%(68/84)、96%(80/83)和99%(83/84)(χ^2=21.469,P<0.001),Ⅲ型分别为100%(84/84)、100%(83/83)和100%(84/84);Ⅰ型脊髓灰质炎病毒抗体GMT分别为1024.00、1015.48和982.61(F=2.742,P=0.066),Ⅱ型分别为16.81、107.94和218.85(F=33.570,P<0.001),Ⅲ型分别为990.75、990.36和613.92(F=37.886,P<0.001)。结论不同脊髓灰质炎基础免疫程序中,sIPV和bOPV在≥2月龄的婴儿中均具有良好的安全性和免疫原性,2sIPV+1bOPV组和3sIPV组较1sIPV+2bOPV组产生更高的Ⅱ型脊髓灰质炎病毒抗体GMT和阳转率,1sIPV+2bOPV组和2sIPV+1bOPV组较3sIPV组产生更高的Ⅲ型脊髓灰质炎病毒抗体GMT。

关键词： 脊髓灰质炎   免疫策略   IPV   bOPV  

摘要： 目的了解哈尔滨市脊髓灰质炎疫苗接种现况,调查儿童家长对IPV-OPV序贯免疫策略知晓及接受情况,为我国无脊灰状态后期制定脊髓灰质炎疫苗免疫策略提供依据。方法收集哈尔滨市2016年5月1日—2018年12月31日脊髓灰质炎疫苗接种个案数据,了解脊髓灰质炎疫苗接种现况;采用随机电话调查,了解720名儿童家长对IPV-OPV序贯免疫策略知晓及接受情况并进行描述性分析。结果哈尔滨市共有162 646名儿童接种脊髓灰质炎疫苗,累计接种624 637剂次,其中,接种bOPV 442 856剂次(70.90%),接种IPV 152 446剂次(24.40%),接种含IPV的五联疫苗29 339剂次(4.70%)。2016—2018年执行IPV-bOPV序贯免疫策略儿童比例依次为79.26%、89.10%和93.30%。电话调查720名儿童家长中,80.28%对IPV-bOPV序贯免疫策略有一定了解,91.39%接受IPV-bOPV序贯免疫策略进行接种。结论哈尔滨市脊灰疫苗免疫策略以IPV-bOPV序贯为主且执行度高,儿童家长对其具有良好的知晓度和接受度。

关键词： 脊髓灰质炎灭活疫苗   二价脊髓灰质炎减毒活疫苗   基础免疫   序贯免疫   免疫原性  

摘要： 目的比较脊髓灰质炎(脊灰)灭活疫苗(Inactivated poliovirus vaccine,IPV)与I+III型二价脊灰减毒活疫苗(Bivalent oral poliovirus vaccine,bOPV)两种序贯基础免疫程序的免疫原性。方法在河北省肥乡区招募健康婴儿,随机分成两组,按2-3-4月龄基础免疫程序分别接种IPV-bOPV-bOPV和IPV-IPV-bOPV,检测基础免疫前和免疫后28-42d血清脊灰病毒Ⅰ、Ⅱ、Ⅲ型中和抗体,分析中和抗体阳性率、阳转率和几何平均滴度(Geometric mean titer,GMT)。结果IPV-bOPV-bOPV、IPV-IPV-bOPV程序组分别招募受试者69名、68名,两组婴儿基础免疫后脊灰病毒中和抗体阳性率分别为Ⅰ型100%、100%,Ⅱ型98.55%、100%,Ⅲ型100%、100%;阳转率分别为Ⅰ型100%、100%,Ⅱ型97.06%、100%(Fisher确切概率法,P>0.05),Ⅲ型100%、100%;GMT增长倍数分别为Ⅰ型758倍、810倍(Z=-0.62,P=0.535),Ⅱ型5倍、26倍(Z=-5.15,P<0.001),Ⅲ型379倍、634倍(Z=-3.34,P=0.001)。结论两种IPV与bOPV序贯基础免疫程序均具有良好的免疫原性;IPV-IPV-bOPV程序对Ⅱ、Ⅲ型脊灰病毒的免疫原性优于IPV-bOPV-bOPV程序。

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   成果奖   全国科学大会   糖丸   人的生命  

摘要： 顾方舟(1926.06-2019.01),浙江宁波人,中国医学科学院北京协和医学院原院长、病毒学专家、教授。他是我国脊髓灰质炎疫苗研发生产的拓荒者、科技攻关的先驱者。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。他曾荣获全国科学大会成果奖和“全国消灭脊髓灰质炎工作先进个人”“人民科学家”等荣誉称号。

关键词： Poliovirus   RACK1   IRES   Translation  

摘要： Viruses have evolved strategies to ensure efficient translation using host cell ribosomes and translation factors. In addition to cleaving translation initiation factors required for host cell translation, poliovirus (PV) uses an internal ribosome entry site (IRES). Recent studies suggest that viruses exploit specific ribosomal proteins to enhance translation of their viral proteins. The ribosomal protein receptor for activated C kinase 1 (RACK1), a protein of the 40S ribosomal subunit, was previously shown to mediate translation from the 5' cricket paralysis virus and hepatitis C virus IRESs. Here we found that translation of a PV dual-luciferase reporter shows a moderate dependence on RACK1. However, in the context of a viral infection we observed significantly reduced poliovirus plaque size and titers and delayed host cell translational shut-off. Our findings further illustrate the involvement of the cellular translational machinery during PV infection and how viruses usurp the function of specific ribosomal proteins.

关键词： Poliovirus receptor   Cytotoxic T lymphocyte-associated antigen 4   Biomarker   Non-small-cell lung cancer   Immunohistochemistry  

摘要： Introduction Poliovirus receptor (PVR) is a tumor promoter and a regulatory checkpoint that enhances immunosuppression. We investigated PVR expression by applying immunohistochemistry (IHC) staining. A positive association existed between PVR expression and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expression in patients with surgically resected non-small-cell lung cancer (NSCLC). PVR expression is a prognosis predictor of lung adenocarcinoma. Purpose To investigate the prognostic significance of PVR expression and CTLA4 expression for surgically resected NSCLC. Patients and methods The medical records of 108 Chinese patients with primary NSCLC who underwent surgery were retrospectively reviewed. The expression of PVR and CTLA4 were measured through IHC. Clinical characteristics, the association between PVR and CTLA4, and the prognostic significance of PVR were analyzed. Results A significant positive association was observed between PVR and CTLA4 expression in NSCLC (P = 0.016). PVR had a high positive rate among females, nonsmokers, and patients with adenocarcinoma and advanced lung cancer. The overall survival (OS) of patients with negative PVR expression was significantly longer than that of patients with positive PVR expression (P = 0.049), especially among females (P = 0.03) and nonsmokers (P = 0.025). Multivariate analysis results showed that advanced tumor stage and PVR expression were independent prognosis predictors of poor OS. Conclusion PVR can potentially serve as a prognostic predictor and biomarker for NSCLC and cancer anti-CTLA4 immunotherapy response.

关键词： poliovirus   live-attenuated vaccine   poliovirus eradication   OPV2   Sabin 2p  

摘要： The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 50 untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.

关键词： 脊髓灰质炎   疫苗   接种异常反应  

摘要： 研究脊髓灰质炎疫苗疑似预防接种异常反应(AEFI)发生特征,对脊灰疫苗的安全性作出分析。方法:对2015—2017年湖北省脊髓灰质炎疫苗预防接种异常反应进行监测,分析不同疫苗的安全性。结果:湖北省2015年-2017年,不同脊灰疫苗类型报告AEFI发生率之间存在显著差异,具体表现为IPV-Sabin报告率最高,tOPV的报告率最低。接种剂次为1中各类型疫苗接种后反应率最高明显大于其他接种剂次,而其他接种剂次对比各种类型疫苗接种后反应率并未呈现出显著差异。结论:湖北省脊髓灰质炎疫苗接种后异常严重反应的发生率较低,疫苗接种安全性良好,但还应该在维持现有安全性的基础上加强对罕见异常反应的控制和研究。

关键词： Affordable IPV   Standalone adjuvanted IPV   Aluminium hydroxide adjuvant   Booster vaccination   Immunogenicity   Polio   Primary vaccination  

摘要： Background: Availability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV. Methods: A phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15-18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre >= 4-fold higher than the estimated maternal antibody titre and a titre >= 8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0). Results: Seroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1);100% vs 100% (type 2);and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined -10%-point limit: 3.94% (-6.51;-2.01) for type 1;0.0% (-1.30;-1.37) for type 2;-0.85 (-2.46;0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV. Conclusions: Non-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated. (C) 2020 The Authors. Published by Elsevier Ltd.

关键词： 三氯生   复方消毒剂   脊髓灰质炎病毒   肠道病毒71型   埃可病毒11型   灭活效果  

摘要： 目的观察一种三氯生复方消毒剂对3种肠道病毒的灭活效果。方法采用悬液定量灭活试验方法,对该复方消毒剂灭活3种肠道病毒的效果进行观察。结果该复方消毒剂含三氯生4000~5000 mg/L与体积分数75%~85%乙醇。以该复方消毒剂原液作用0.5 min,对悬液内脊髓灰质炎病毒I型、肠道病毒71型和埃可病毒11型平均灭活对数均>4.00。结论该复方消毒剂原液对3种肠道病毒具有快速灭活效果。