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。     

sIPV process development for costs reduction

Polio is expected to be eradicated within only a few years from now. Upon polio eradication, the use of oral polio vaccines, which can cause circulating and virulent vaccine derived polio viruses, will be stopped. From this moment onwards, inactivated polio vaccines (IPV) will be used for worldwide vaccination against polio. An increased demand for IPV is thus anticipated. As a result, process development studies regarding the IPV production process, developed in the 1960s, have intensified. Studies on yield optimization aiming at costs reduction as well as the use of alternative polio viruses, which are more biosafe for manufacturing, are actual. Here our strategy to setup a new IPV production process using attenuated Sabin polio virus strains is presented. Moreover, aspects on reduction of the costs of goods and the impact of process optimization on sIPV costs are reviewed.     

两种方法对Ⅰ型Sabin株脊髓灰质炎病毒神经毒力的共同评价

目的 研究PCR和限制性内切酶分析突变（mutant analysis by PCR and restriction enzyme cleavage,MAPREC）技术和猴体神经毒力试验（monkey neurovirulence test,MNVT）评价同一批Ⅰ型Sabin株脊灰病毒神经毒力的结果差异。方法 采用MAPREC技术,检测Ⅰ型Sabin株脊灰病毒神经毒力关键位点480和525位点突变率;采用MNVT病理切片分析,评价Ⅰ型Sabin株脊灰病毒神经毒力。结果 MAPREC检测待测样品核酸480和525位点突变率均值为0.460%,低于高突变参考品的1.288%。MNVT切片结果分析表明,有效猴病变分值差合格。结论 对同一批样品,MAPREC与MNVT分析结果一致。     

A comparative study between outbred and inbred rat strains for the use in in vivo IPV potency testing

In vivo potency testing of inactivated poliovirus vaccines (IPV) is generally performed in rats, although no systematic investigation has identified the most appropriate rat strain for anti-poliovirus antibody quantification. We investigated humoral immune responses to IPV in five different rat strains to identify the most suitable strain. Three outbred (Wistar, Wistar Hannover, Sprague-Dawley) and two inbred rat strains (Fisher 344, Wistar Furth) were immunized intramuscularly with a full or one-fifth human dose of commercial IPV. Anti-poliovirus neutralizing antibody (NA) titers were measured using Salk and Sabin virus neutralizing assays. Post-vaccination responses varied between strains; inbred strains showed greater animal-to-animal variation in NA responses than outbred strains. Virus NA titers persisted for 9 weeks with little reduction in the response. The outbred Wistar rat model was identified as the preferred strain for IPV potency testing based on its capacity to produce high, dose-dependent anti-poliovirus NA responses, with low animal-to-animal variation.     

Benefit of social media on patient engagement and satisfaction: Results of a 9-month,qualitative pilot study using Facebook

Background

Despite the potential benefits of social media, health care providers are often hesitant to engage patients through these sites. Our aim was to explore how implementation of social media may affect patient engagement and satisfaction.

Vaccine derived bi- and multi-recombinant Sabin strains

A retrospective analysis of five Sabin intertypic recombinant strains, isolated from human feacal specimens during the time period 1978–1985 in Greece, was performed by RT-PCR, Restriction Fragment Length Polymorphism (R.F.L.P.) and sequencing. Of the studied strains, three (EPA, EPB, EPC) were found to be bi-recombinant Sabin3/Sabin2/Sabin3 (S3/S2/S3), one strain was characterized as a probable S3/S2- CAV18 or CAV21-S2/S1 multi-recombinant (EDP11) and one was identified as a tripartite one S3/S2/S1 (EDP12). Samples EPA, EPB and EPC presented a common recombination junction in the 2C genomic region. Moreover, strains EPA and EPB shared also the second recombination site in the 3D genomic region, whereas the second recombination of EPC was also determined in 3D but in a different nucleotide position. Strains EDP11 and EDP12 presented both identical recombination motifs and recombination sites. The first was detected in the 2C genomic region and the second in the 3D region. Strain EDP11 presented an interesting feature since a sequence of 120 nucleotides seems to have derived from a member of human enteroviruses species C (CAV18 or CAV21). This finding is of great importance, considering that this strain (EDP11) was isolated from an area and time period, where no Coxsackie A virus or poliovirus epidemics occurred. Our study underlines the role of specific positions and motifs of the poliovirus genomic sequences involved in recombination events and prompts that Coxsackie A viruses belonging to human enterovirus species C (genetically closely related to PV) are considered as the possible counterparts of the recombination.     

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.     

Immunogenicity and safety of different sequential schedules of Sabin strain-based inactivated poliovirus vaccination: A randomized,controlled, open-label,phase IV clinical trial in China

BackgroundThe immunogenicity and safety of the sequential schedule of Sabin strain-based inactivated poliovirus vaccine (sIPV) and bivalent oral poliovirus vaccine (bOPV) remains poorly understood in Chinese population.MethodsA multi-center, open-label, randomized controlled trial was performed involving 648 healthy infants aged 2 months from Inner Mongolia, Shanxi, and Hebei provinces. These participants were divided into three groups: sIPV-bOPV-bOPV, sIPV-sIPV-bOPV, and sIPV-sIPV-sIPV. Doses were administered sequentially at age 2, 3, and 4 months. Neutralisation assays were tested using sera collected at 2 months and 5 months.ResultsA total of 569 were included in the per-protocol analysis. The seroconversion rates of poliovirus type 1 and 3 were 100% in all three groups, the seroconversion rate of poliovirus type 2 was 91.53% (173/189) (95% CI: 86.62–95.08) in the sIPV-bOPV-bOPV group, 98.38% (182/185) (95% CI: 95.33–99.66) in the sIPV-sIPV-bOPV group, and 99.49% (194/195) (95% CI: 97.18–99.99) in the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus types 1 and 3, the sIPV-bOPV-bOPV and sIPV-sIPV-bOPV groups were non-inferior to the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus type 2, the sIPV-sIPV-bOPV group was non-inferior to the sIPV-sIPV-sIPV group, and the sIPV-bOPV-bOPV group was inferior to the sIPV-sIPV-sIPV group. All three groups exhibited good safety, with two serious adverse events reported, that were unrelated to vaccine.ConclusionsIn china, a new vaccination schedule that including 2 doses of IPV in the national immunization programs is essential.Trial registration ClinicalTrials.govNCT04054492.     

Safety and immunogenicity of experimental stand-alone trivalent,inactivated Sabin-strain polio vaccine formulations in healthy infants: A randomized,observer-blind,controlled phase 1/2 trial

BackgroundTo increase the global supply of affordable IPV vaccine, preferably using Sabin viruses to comply with GAPIII requirements, Takeda has assessed three dosages of a stand-alone sIPV.MethodsIn this phase I/II study two cohorts of 40 adults and 60 toddlers, respectively, were initially assessed for safety after receiving high-dosage sIPV compared with placebo (adults) or Salk IPV (toddlers). A cohort of 240 infants was then enrolled and randomized (1:1:1:1) to receive low-, medium- or high-dosage sIPV, or a reference Salk IPV in a three-dose primary schedule at 6, 10 and 14 weeks of age. Parents completed safety diaries for 4 weeks after each dose, and immunogenicity was measured as neutralization antibody titers at baseline and four weeks after vaccination.ResultsAll vaccinations were generally well-tolerated and sIPV had a comparable safety profile to the control arm in adults or the reference Salk IPV vaccine in toddlers and infants. Infants displayed dosage-dependent immune responses to sIPV when assayed using Sabin strains, which were equivalent to the reference IPV in the high-dosage sIPV group for serotypes 1 and 2, but not for Sabin and Salk serotype 3. Seroconversion rates (SCR) of the low- and medium-dosage groups were significantly lower than the Salk IPV group for both Sabin and Salk serotypes 1 and type 2 (p < 0.05), with no significant differences for Salk or Sabin serotypes 3. Responses to sIPV, particularly to Sabin types 1 and 2, were higher in initially seronegative infants, indicating possible interference by maternally-derived antibodies.ConclusionsA novel stand-alone Sabin-based IPV vaccine was well tolerated with an acceptable safety profile, but less immunogenic than reference Salk IPV at 6, 10 and 14 weeks of age for Salk serotypes 1 and 2, with apparent interference by maternal antibodies. Additional preclinical assessments will be made before any further clinical development.     

Eculizumab and Belatacept for De Novo Atypical Hemolytic Uremic Syndrome Associated With CFHR3-CFHR1 Deletion in a Kidney Transplant Recipient: A Case Report

Background

Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway.