Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation,an open label,phase IV,randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age.MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age.FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C.InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.     

Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan

Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan, between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1 vaccine-derived strains, using mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have marked neurovirulence. Some of the neutralizing antigenic sites, temperature sensitivity, and plaque-forming ability of two virulent vaccine-derived poliovirus strains were similar to Mahoney strain. The neutralizing activity of human sera obtained after oral poliomyelitis vaccine (OPV) administration against one of the virulent vaccine-derived polioviruses was examined. Although all human sera showed sufficient neutralizing activity for the prevention of poliomyelitis by vaccine-derived poliovirus strains, a lower titer than that against Sabin type 1 strain was observed. Vaccination against virulent vaccine-derived poliovirus will be effective. However, the environmental presence of viruses that have properties similar to those Mahoney strain is a threat. The introduction of inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together with reinforced environmental surveillance is important for the final phase of the polio eradication program by the World Health Organization (WHO).     

A comparison of three methods for titration of poliovirus vaccines

Two methods for in vitro endpoint titration of poliovirus — the roller tube and the microtitration assay — were compared with each other and with the plaque assay, using secondary vervet monkey kidney cells and Vero cells as indicators. The roller tube method is the most reliable under difficult working conditions, but is otherwise cumbersome and expensive. The microtitre method is the most economical and the plaque assay the most sensitive. By suspending freshly trypsinized indicator cells with the virus dilutions before planting, it was possible to simplify the microtitre method considerably. The sensitivity of the plaque assay was improved for Vero cells by absorbing the virus onto freshly planted monolayers. The method was scaled down to a semi-micro level by using 24-well cell culture trays. The slower rate of plaque development under a low calcium overlay medium facilitated a more accurate plaque count.     

A simple quantitative protein A micro-immunoprecipitation method; assay of antibodies to the N and H antigens of poliovirus

Staphylococcus aureus (Cowan strain I) was used to absorb immune complexes from antiserum to poliovirus to which labeled N or H poliovirus antigens had been added, and the radioactivity in the pelleted organisms and in the supernatant was measured. Excellent agreement was obtained between values calculated separately from the pellet and supernatant readings, validating the use of supernatant measurements from a microtitration plate method.     

PEG6000沉淀结合差速离心方法浓缩水中脊髓灰质炎病毒

建立一种简便,有效的从细菌培养物中纯化ＰＶ１病毒的方法用于水病毒消毒实验。方法ＰＶ１Ｈｅｎａｎ株在Ｈｅｐ－２细胞中增殖后用聚乙二醇６０００沉淀结合差速离心的方法纯化病毒,ＲＴ－ＰＣＲ和透射电镜鉴定提纯病毒的形态学和分子生物学特性。结论ＰＥＧ６０００结合差速离心的方法较之蔗糖密度梯度区带离方法易于操作且比单独ＰＥＧ沉淀有更高的纯化系数,是一种简便,有效的方法。     

Ⅰ型疫苗衍生脊髓灰质炎病毒循环的发现和基因特点

目的分析贵州省2004年Ⅰ型循环的疫苗衍生脊髓灰质炎(脊灰)病毒(cVDPVs)的基因特征,阐述cVDPVs的出现为全球消灭脊灰带来的挑战。方法2004年中国疾病预防控制中心(CDC)病毒病预防控制所国家脊灰实验室对各个省送检的每1个脊灰病毒分离株进行聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)和酶联免疫吸附试验(ELISA)两种方法的型内鉴定。毒株型内鉴别显示异常时,则对该株病毒进行VP1编码区全基因的序列测定和分析。结果2004年从贵州省CDC送检的脊灰病毒株(或粪便标本的复核)中,共发现9株Ⅰ型疫苗衍生脊灰病毒(VDPVs)。这9株VDPVs从2例急性弛缓性麻痹(AFP)病例和4名接触者的粪便标本中分离到。其中8株分离于贞丰县挽兰乡的2例AFP病例和3名接触者,另外1株分离于贞丰县白层镇的1名AFP病例接触者。结论对9株cVDPVs的VP1编码区的序列测定和分析证实,它们有相似的核苷酸序列,共享5个核苷酸突变位点,说明VDPVs已发生了循环。cVDPVs很可能来源于2003年秋季的1次口服脊灰减毒活疫苗病毒的传播。对其中5株VDPVs的3D区和1株VDPV(8229-2)的全序列测定和分析,未发现脊灰病毒血清型之间的重组,也未发现与非脊灰肠道病毒的重组。     

贵州省2004年分离到的脊髓灰质炎病毒分子生物学特征

目的研究贵州省2004年分离到的脊髓灰质炎(脊灰)病毒分子生物学特征。方法对贵州省2004年分离到的所有脊灰病毒,用聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)和酶联免疫吸附试验(ELISA)法进行了型内鉴定,并对型内鉴定异常株进行了VP1区的序列测定。结果贵州省在2004年急性弛缓性麻痹(AFP)病例及接触者、流动人口和健康儿童的粪便标本中,共有95例分离到脊灰病毒。其中Ⅰ型22例,Ⅱ型26例,Ⅲ型21例,混合型19例,脊灰病毒混合非脊灰肠道病毒7例。经用PCR-RFLP和ELISA方法进行型内鉴定,共有16株病毒与疫苗株病毒存在差异,其中3株脊灰病毒与疫苗株病毒在PCR-RFLP图谱上有差异[其中1株同时为双反应(DRV)],3株ELISA结果为DRV,11株ELISA结果为非疫苗类似株(NSL)。在这些型内鉴定异常株病毒中,Ⅰ型13株,Ⅱ型3株。对这16株脊灰病毒进行VP1区序列测定,发现9株Ⅰ型疫苗衍生脊灰病毒(VDPV)和1株Ⅱ型VDPV。结论根据对贵州省2004年从95例AFP病例及接触者、流动人口、健康儿童分离的脊灰病毒的血清定型结果和型内鉴定结果及对13株Ⅰ型和8株Ⅱ型脊灰病毒VP1区核苷酸序列测定证实,脊灰减毒活疫苗病毒在人群的循环导致疫苗病毒神经毒力恢复突变。通过AFP病例监测系统及时发现了Ⅰ型VDPV的循环和Ⅱ型VDPV。对2004年下半年脊灰病毒基因特点的分析,提示贵州省已经阻断了Ⅰ型VDPV的循环。     

Prevention of pertussis across the age spectrum through the use of the combination vaccines PENTACEL™ and ADACEL™

Acellular pertussis-containing combination vaccines are widely used in the developed world for the control of pertussis and have been successful in controlling disease in preschool-aged children. Combination vaccines formulated for use in adolescents and adults have been developed more recently and are increasingly being implemented for the control of pertussis in these age groups. One such family of products is PENTACEL? (Haemophilus influenzae type b conjugate vaccine reconstituted with component pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine, DTaP-IPV-Hib), for use in young children, and ADACEL? (tetanus and diphtheria toxoids adsorbed combined with component pertussis vaccine, dTap) for use in adolescents and adults. These products have been demonstrated to be safe, immunogenic and effective for the control of pertussis and the other included diseases.     

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。     

New insights into physiopathology of immunodeficiency-associated vaccine-derived poliovirus infection; systematic review of over 5 decades of data

Widespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV).We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients’ outcomes. Study protocol was registered with PROSPERO (CRD42016052931).4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p < .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p < .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients’ survival.With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions.