Glutathione is a highly efficient thermostabilizer of poliovirus Sabin strains

Glutathione (GSH) is the most abundant thiol peptide in animal cells and has a critical role in antioxidation. GSH was reported to be essential for stabilization of some enteroviruses, including poliovirus (PV), during viral morphogenesis. Here, we explored the potential use of GSH as a thermostabilizer of oral poliomyelitis vaccine (OPV) formulations. GSH significantly protected the three types of PV from heat-inactivation in a concentration-dependent manner. At a GSH concentration of 20 mM, nearly complete protection was observed against heating temperatures up to 53 °C for 2 min. GSH also markedly protected PV1 from heat-inactivation and this up to 6 h at temperatures of 44 °C and 46 °C and 3 h at 48 °C. The fact that GSH is naturally present at high concentration in the human body makes it an efficient candidate stabilizer for OPV formulations.     

脊髓灰质炎病毒细胞系敏感性实验方法的建立

目的评价中国疾病预防控制中心(CDC)病毒病预防控制所国家脊髓灰质炎(脊灰)实验室所用细胞系对脊灰病毒的敏感性,制备国家脊灰实验室质量控制株(China Sabin Master Reference,CSMR)和用于脊灰实验室网络的中国Sabin参考株(China Sabin Test Reference Strain;CSTRS),提供给省级CDC脊灰实验室用于其对所使用的RD-A、L20B细胞系的敏感性评价。方法96孔微量培养板滴定法。结果国家脊灰实验室CSMR 3次独立的细胞敏感性实验结果的滴度波动在±0.5log10,同时用英国国家生物标准品与控制样品研究所(NIBSC)提供的已知滴度Sabin脊灰病毒参考株(NIBSC原始株)作平行对照,NIBSC原始株3次滴度结果与其本身提供的参考值相比较,其滴度波动也均在±0.5log10。结论通过NIBSC原始株3次滴度结果作平行对照,证实中国CSMS结果符合实验要求,国家脊灰实验室的内部CSMR结果有效;从而制定了国家脊灰实验室质量控制参考株的滴度参考值,表明国家脊灰实验室所用细胞系的敏感性未下降,实验程序无误。CSTRS可作为标准株分发到省级CDC脊灰实验室用于进行细胞系敏感性实验。     

后脊髓灰质炎时代我国应用赛宾株灭活脊髓灰质炎疫苗免疫的可行性

在所有国家被证实全部阻断了脊髓灰质炎(脊灰)野病毒传播后,全球将停止使用口服脊灰减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)免疫,进入后脊灰时代。为此,世界卫生组织(WHO)提出了届时全面停止OPV的使用,并同步开始灭活脊灰病毒疫苗(Inactivated Poliovirus Vaccine,IPV)的免疫,发展中国家更应考虑应用廉价的赛宾(Sabin)株IPV(sIPV)免疫,直至最终根除脊灰。然而目前全球尚无开发成功的sIPV上市。现介绍WHO推荐的这一免疫策略,分析全球sIPV的研发现状,从免疫策略、免疫程序、生产技术、疫苗供应等方面探讨我国应用sIPV免疫的可行性。鉴于这些可行性,我国应尽快推进sIPV的研发进程,为脊灰免疫策略的调整、实施做好准备。     

La batalla de Madrid por las vacunas antipoliomielitis (1963): ciencia,ideología y poder en la primera campaña de inmunización masiva en España

Between 1958 and 1963, Spain witnessed the highest ever incidence of poliomyelitis (2000 cases and 200 deaths per year). Although Salk's inactivated vaccine had arrived in Spain in 1957, the government took no decisive action to administer it to the entire population at risk. Neither was Sabin's attenuated vaccine administered, available in Europe from 1960. While other countries adopted one or the other, in Spain rivalry arose over the two vaccines, with mixed results. The Salk vaccine was administered to a small percentage of the population at risk through the Compulsory Sickness Insurance scheme (Spanish initials: SOE), while at the same time a research team at the National School of Health led by Florencio Pérez Gallardo (1917-2006) carried out a model epidemiological study that demonstrated the superiority of the Sabin vaccine. In 1963, the SOE launched a national campaign with the Salk vaccine promoted by the paediatrician Juan Bosch Marín (1902-1995), a representative of the most conservative structure of the Franco regime. The dispute over which vaccine was best reached its peak in early 1963 at various scientific conferences in Madrid. Bosch Marín's group argued in favour of his campaign and the Salk vaccine, while Pérez Gallardo did the same for the oral vaccine, achieving a substantial impact by inviting Sabin himself to speak. By the end of the year, following a pilot study, the first mass oral vaccination campaign against polio was introduced in Spain.     

Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: A phase II,randomized, dose-finding trial

BackgroundIn order to completely eradicate polio caused by wild poliovirus infection as well as vaccine-associated paralytic polio (VAPP), Sabin inactivated poliovirus vaccine (sIPV) should be developed to meet the requirements for biosafety and affordable strategy in the developing countries.MethodA randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety among infants aged 2 months (60–90 days) receiving five different vaccination regimens: the test groups (A, B, and C) received three doses of sIPV with high, medium, and low D antigen content, respectively, on the month 0, 1, 2 schedule; two control groups (D and E) received three doses of conventional IPV (cIPV) or sIPV (CAMS), respectively, on the same schedule as that of test groups. Serum samples were collected immediately before the 1st dose and 30 days after the 3rd dose vaccination to assess the immunogenicity. Adverse events occurring within 30 days after each dose were collected to assess the safety.ResultsAfter three doses, seroconversion rates in groups A–E were 100%, 98.2%, 100%, 100%, and 100%, respectively, for type 1; 99.1%, 100%, 98.1%, 100%, and 97.1%, respectively, for type 2; and 100%, 100%, 100%, 100%, and 99.0%, respectively, for type 3. The seropositive rates (≥1:8) of groups A–E for all types were nearly 100%. The GMTs in the target dose group (group B) were 4635, 342, and 2218 for type 1–3, respectively. The most common injection-site and systemic adverse reactions were swelling and fever respectively. The swelling (4.2%, P = 0.0075) and fever (58.3%, P = 0.0188) frequency of group A were statistically significantly higher than any other groups.ConclusionThe test sIPV generally demonstrated good safety and immunogenicity. The medium-D antigen dose would be a preferred choice for the further phase III clinical trial in consideration of its high immunogenicity for all serotypes and the satisfying tolerance.Clinical Trials Registration. NCT02985320.     

河北省脊髓灰质炎实验室细胞系敏感性实验方法的建立

目的评价河北省疾病预防控制中心脊髓灰质炎(脊灰)实验室所用细胞系对脊灰病毒的敏感性,制备河北省脊灰实验室质量控制的标准毒株(QC)。方法96孔微量培养板滴定法。结果河北省脊灰实验QC3次独立的细胞敏感性实验结果的滴度波动±0·5log10CCID50,同时用中国疾病预防控制中心病毒病预防控制所国家脊灰实验室提供的已知滴度的中国sabin参考株(ChinaSabinTestReferenceStrain;CSTRS)作平行对照,CSTRS株3次滴度结果与其本身提供的参考值相比较,其滴度波动也均在±0·5log10CCID50。结论河北省脊灰实验室QC结果符合实验要求,脊灰实验室所用细胞系对脊灰病毒的敏感性未下降。     

Immunogenicity and safety of sabin-strain based inactivated poliovirus vaccine replacing salk-strain based inactivated poliovirus vaccine: An innovative application of different strain-IPVs replacement

BackgroundA 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.MethodsWe 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.ResultsOf 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).ConclusionsThe Salk-Sabin-Sabin IPV immunization schedule is not inferior to the Salk-Salk-Salk IPV schedule in terms of both immunogenicity and safety.Clinical trial number: NCT04051736.