江苏省脊髓灰质炎实验室细胞系敏感性实验方法的建立和监测

目的评价江苏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,制备江苏省脊灰实验室的标准毒株（QC）。方法采用96孔微量培养板滴定法。结果江苏省脊灰实验QC3次独立的细胞敏感性实验结果的滴度波动为±0．5 log 10CCID50,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Sabin参考株（China Sabin Test Reference Strain;CSTRS）做平行对照,CSTRS株3次滴度结果与其本身提供的参考值相比较,其滴度波动也均为±0．5细10CCID50。结论江苏省脊灰实验室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。是敏感、有效的。     

Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan

During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains.     

The fight against poliomyelitis through the history: past,present and hopes for the future. Albert Sabin's missing Nobel and his “gift to all the world's children”

Polio, or poliomyelitis, is a disabling and life-threatening disease caused by three poliovirus (PV) serotypes. The virus spreads from person to person and can infect a person’s spinal cord, causing paralysis. In 1988, when the WHO registered 350,000 cases of poliomyelitis in the world and 70,000 which occurred in Africa alone, global poliomyelitis eradication was proposed by the World Health Organization to its member States. On 25 August 2020, while the world was waging war against the Coronavirus pandemic, a historic milestone was reached: Africa was officially declared polio-free.It is an important result obtained thanks to an intensive large-scale vaccination campaign.The road was far from smooth, nevertheless, according to the WHO, a great effort needs to be made in order to facilitate access to vaccination and to promote its implementation in those countries where coverage is low and vaccine hesitancy is high because the risk of the spread of poliomyelitis is still relevant. Eradication of the virus in Africa provides us with an excellent opportunity to commemorate the many scientists who contributed to achieving this epoch-making goal: first of all, Jonas Salk, who developed a killed-virus vaccine in 1952, and, especially, Albert Sabin, who in 1961 launched programs of mass immunisation with his oral vaccine against poliomyelitis.     

Postdonation Anemia in Living Kidney Donors

Background

The effect of nephrectomy on development of anemia in living kidney donation has not been well studied. We hypothesized that the remaining kidney volume and function after donation are determinants of hemoglobin (Hb) concentration and postdonation anemia (PDA).

Effects of the thermal denaturation of Sabin-derived inactivated polio vaccines on the D-antigenicity and the immunogenicity in rats

The efficacy of a Sabin-derived inactivated polio vaccine (sIPV) can be evaluated by measuring the immunogenicity and the contents of D-antigens, which induce the neutralizing antibodies. The immunogenic potency test in rats was done as a national assay in Japan. The two manufacturers of sIPV in Japan have performed both assays since development, and there is no clear discrepancy between the results obtained in the two assays. To further know the relationship between the two assays, we analyzed the effects of the heat treatment of sIPV on the D-antigenicity and the immunogenicity. We observed that the marginal D-antigen that remained after the thermal treatment was capable of inducing relatively high neutralizing antibodies in rats. This indicates that the measurement of the D-antigen contents as part of the quality control of sIPV is more sensitive and appropriate to detect denatured vaccines.     

Cost of achieving equivalent outcomes in sicker patients after liver transplant

Background

We aimed to characterize variability in cost after straightforward orthotopic liver transplant (OLT).

Evaluation of the genetic stability of Sabin strains and the consistency of inactivated poliomyelitis vaccine made from Sabin strains using direct deep-sequencing

Inactivated poliomyelitis vaccine made from Sabin strains (sIPV) has been encouraged to introduce in the “Global Polio Eradication & Endgame Strategic Plan” and increasingly used worldwide. Attenuated Sabin strains used in manufacture of oral poliovirus vaccine (OPV) and sIPV may regain full or partial neurovirulence during growth in vaccine recipients and the vaccine manufacturing processes. Ensuring the molecular consistency of sIPV batches and that no mutation accumulates beyond the level present in past batches are important for quality control of vaccine manufacture process. Direct deep-sequencing allows the construction of a library of virus RNA and the detection of genetic mutations throughout the viral genome. In the present study, direct deep-sequencing was conducted to detect molecular mutations in virus passages, multiple sIPV monovalent lots, and virus monovalent lots from different polio type III strains. The results indicated that direct deep-sequencing can be used to identify and quantify small amounts of mutant viruses in vaccine preparations, trace the source of a specific virus seed, and monitor the batch-to-batch consistency of vaccines, suggesting that this technique could be suitable for the quality control and consistency monitoring of sIPV production.     

Capto Core 400和Sepharose 6FF在Sabin株脊髓灰质炎病毒纯化工艺的应用与比较

目的 分别用新型复合型层析介质Capto Core 400和传统介质Sepharose 6FF纯化Sabin株脊髓灰质炎病毒（Sabin strain poliovirus,sPV）去除宿主细胞蛋白（host cell protein,HCP）和DNA,并且比较纯化结果及工艺参数。方法  用Capto Core 400与Sepharose 6FF纯化Vero细胞培养的Ⅰ、Ⅱ、Ⅲ型sPV浓缩液。分别检测纯化后sPV的D抗原含量、HCP残留量和DNA残留量,计算D抗原回收率、HCP和DNA去除率。结果 Capto Core 400与Sepharose 6FF纯化Ⅰ、Ⅱ、Ⅲ型sPV的D抗原回收率差异均无统计学意义(t值分别为1.09、1.08、1.02,P值均>0.05),但前者的Vero细胞HCP(t值分别为3.15、3.23、3.54)和DNA去除率均高于后者(t值分别为3.41、3.25、3.62),且差异有统计学意义（P值均小于0.05）Capto Core 400与Sepharose 6FF的介质使用体积比为1/20,上样后纯化时间比为1/25,工作缓冲液使用量比为1/4,工艺线性流速比为10,每升介质上样量比为20,最大耐压力比为2。结论  对比Sepharose 6FF,Capto Core 400可以更有效地去除Vero细胞HCP与DNA,各个工艺参数得到了优化,提高了sPV层析纯化的工作效率,并节约时间和成本。     

Immunogenicity and safety of the inactivated poliomyelitis vaccine made from Sabin strains in a phase IV clinical trial for the vaccination of a large population

As a recently launched novel vaccine used as one of the vaccines for the final eradication of polios worldwide, complete data on the consistency and immunogenicity characteristics of the inactivated poliomyelitis vaccine made from the Sabin strain (sIPV) and its safety in large-scale populations are required to support the future use of this vaccine worldwide. A phase IV clinical trial was conducted to perform an immunogenicity evaluation of lot-to-lot consistency of three commercial batches of sIPV in 1200 infants and to investigate the vaccine’s safety on a large-scale in 20,019 infants for active monitoring and 29,683 infants for passive monitoring through the Adverse Event Following Immunization (AEFI) reporting system in China. In the immunogenicity evaluation, the average seroconversion rates for type I, type II and type III of the three groups were 99.83%, 98.93% and 99.44%, respectively. No differences in the seroconversion rate and the GMT ratios were noted in the pair-to-pair comparisons. In the large-scale safety evaluation, most adverse reactions occurred 0–30 days after the first doses, and the common local and systemic reactions were similar to those in the phase III clinical trial, with low incidence in both activated and passive monitoring. In conclusion, sIPV exhibits good lot-to-lot consistency and safety in large-scale populations; thus, it is qualified to serve as one of the vaccines for use in eradicating all wild and vaccine-derived polioviruses worldwide in the near future.Clinic Trial Registration. NCT04224519 and NCT04220515.     

Evaluating cessation of the type 2 oral polio vaccine by modeling pre- and post-cessation detection rates

The globally synchronized removal of the attenuated Sabin type 2 strain from the oral polio vaccine (OPV) in April 2016 marked a major change in polio vaccination policy. This change will provide a significant reduction in the burden of vaccine-associated paralytic polio (VAPP), but may increase the risk of circulating vaccine-derived poliovirus (cVDPV2) outbreaks during the transition period. This risk can be monitored by tracking the disappearance of Sabin-like type 2 (SL2) using data from the polio surveillance system. We studied SL2 prevalence in 17 countries in Africa and Asia, from 2010 to 2016 using acute flaccid paralysis surveillance data. We modeled the peak and decay of SL2 prevalence following mass vaccination events using a beta-binomial model for the detection rate, and a Ricker function for the temporal dependence. We found type 2 circulated the longest of all serotypes after a vaccination campaign, but that SL2 prevalence returned to baseline levels in approximately 50 days. Post-cessation model predictions identified 19 anomalous SL2 detections outside of model predictions in Afghanistan, India, Nigeria, Pakistan, and western Africa. Our models established benchmarks for the duration of SL2 detection after OPV2 cessation. As predicted, SL2 detection rates have plummeted, except in Nigeria where OPV2 use continued for some time in response to recent cVDPV2 detections. However, the anomalous SL2 detections suggest specific areas that merit enhanced monitoring for signs of cVDPV2 outbreaks.