关键词： polio   OPV   shedding   immunity   HIV   infants   vaccine   VDPV  

摘要： Background. With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. Methods. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. Results. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0-2 OPV doses but significantly higher in the HIV-infected versus uninfected children after >= 3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. Conclusions. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.

关键词： Polio   Vaccination   Intradermal   Needle-free   Jet injector  

摘要： For global eradication of poliomyelitis, inactivated poliovirus vaccine (IPV) needs to become available in all countries. Using fractional-doses (reduced-doses) may impact affordability and optimize the utilization of the production capacity. Intradermal administration has the potential to lower the dose without reducing immunogenicity. A needle-free jet injector may be a reliable way to administer vaccines intradermally. The primary objective of this randomized controlled trial was to compare the immunogenicity and tolerability of fractional-dose intradermal IPV (Netherlands Vaccine Institute, NVI) booster vaccination administered with a jet injector (PharmaJet) to full-dose and fractional-dose intramuscular vaccination with a needle and syringe. Immunogenicity was assessed by comparing the differences in the post-vaccination log(2) geometric mean concentrations of neutralizing antibodies (GMC) between the study groups. A total of 125 Dutch adult volunteers with a well-documented vaccination history were randomized to one of four groups: full-dose intramuscular needle (IM-NS-0.5), full-dose intramuscular jet injector (IM-JI-0.5), 1/5th dose intramuscular needle (IM-NS-0.1), 1/5th dose intradermal jet injector (ID-JI-0.1). Vaccination with the JI was less painful (87% no pain) than vaccination with a NS (60% no pain), but caused more transient erythema (11 85%, NS 24%) and swelling (11 50%, NS 5%). Intradermal vaccination caused less vaccination site soreness (ID 16%, IM 52%). At baseline all subjects had seroprotective antibody concentrations. After 28 days, GMC were slightly lower in the ID-JI-0.1 group than in the reference group (IM-NS-0.5). The differences were not statistically significant, but the stringent non-inferiority criterion (i.e. a difference of 1 serum dilution in the microneutralization assay) was not met. After one year, differences in GMC were no longer apparent. In contrast, intramuscular vaccination with a fractional dose administered with a ne

关键词： 脊髓灰质炎疫苗   健康人群   湖北省   免疫效果分析   免疫水平监测   脊灰减毒活疫苗   免疫成功率   抗体水平  

摘要： 为了解湖北省健康人群脊髓灰质炎抗体水平和免疫成功率情况,评价口服脊灰减毒活疫苗（Oral Poliomyelitis At-tenuated Live Vaccine,OPV）预防接种的质量和效果,于2010年抽取湖北省A县开展健康人群脊髓灰质炎免疫水平监测,并在湖北省B县开展了脊灰疫苗免疫成功率监测。

关键词： 脊髓灰质炎疫苗   强化免疫活动   效果评价  

摘要： 目的评价2012年四川省西部的阿坝、甘孜、凉山地区开展儿童脊髓灰质炎疫苗强化免疫活动效果,为今后继续维持无脊髓灰质炎工作提供依据。方法 2012年按照脊髓灰质炎强化免疫活动实施方案在阿坝、甘孜、凉山地区开展了3轮脊灰疫苗强化免疫活动,并进行了每轮服苗结束后接种率现场快速评估和脊灰疫苗接种后目标儿童血清抗体水平监测。结果 3轮脊灰强免报告接种率分别为97.54%、97.77%和96.94%,均达到了95%以上的目标。共报告零剂次儿童15 583人,零剂次儿童主要集中在0～1岁组(51.71%),大于1岁年龄段儿童的零剂次比例明显下降。3轮快速评估接种率分别为99.53%、98.42%和97.96%。接种1个月后,0～14岁儿童脊灰抗体阳性率97.70%。结论该次强免活动疫苗接种率较高,接种效果较好,0～14岁儿童对脊髓灰质炎建立了比较牢固的免疫屏障。但零剂次儿童的存在,提示常规免疫工作中有薄弱环节,免疫空白仍然存在。儿童完成全程免疫是保证免疫效果的基础,强化免疫只能是一种对常规免疫的补充,不能以强化免疫代替常规免疫,建立可持续发展的免疫规划仍是目前工作的重点。

关键词： Innate immune response   interferons   poliomyelitis   RLRs   Sabin attenuated virus   TLRs  

摘要： Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon alpha/beta at early time point of infection. The induced expression of IFN alpha/beta gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

关键词： Biology   Evolutionary biology   Evolutionary genetics   Genome evolution   Genomics   Immunodeficiency viruses   Infectious diseases   Infectious diseases of the nervous system   Medicine   Microbiology   Poliomyelitis   Research Article   Viral diseases   Viral evolution   Virology  

摘要： Vaccine derived poliovirus (VDPV) type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003-2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s) of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5UTR, P1, P2, P3, and 3'UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV), including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1) individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2) genetic divergence of VDPV strains may remain extensive during years long replication in humans.

关键词： helical reconstruction   ghost reflection   membrane   oligomerization   cryo-electron microscopy  

摘要： The poliovirus RNA-dependent RNA polymerase, 3Dpol, replicates the viral genomic RNA on the surface of virus-induced intracellular membranes. Macromolecular assemblies of 3Dpol form linear arrays of subunits that propagate along a strong protein-protein interaction called interface-I, as was observed in the crystal structure of wild-type poliovirus polynnerase. These "filaments" recur with slight modifications in planar sheets and, with additional modifications that accommodate curvature, in helical tubes of the polymerase, by packing filaments together via a second set of interactions. Periodic variations of subunit orientations within 3Dpol tubes give rise to "ghost reflections" in diffraction patterns computed from electron cryomicrographs of helical arrays. The ghost reflections reveal that polymerase tubes are formed by bundles of four to five interface-I filaments, which are then connected to the next bundle of filaments with a perturbation of interface interactions between bundles. While enzymatically inactive polymerase is also capable of oligomerization, much thinner tubes that lack interface-I interactions between adjacent subunits are formed, suggesting that long-range allostery produces conformational changes that extend from the active site to the protein-protein interface. Macromolecular assemblies of poliovirus polymerase show repeated use of flexible interface interactions for polymerase lattice formation, suggesting that adaptability of polymerase-polymerase interactions facilitates RNA replication. In addition, the presence of a positively charged groove identified in polymerase arrays may help position and stabilize the RNA template during replication. (C) 2013 Elsevier Ltd. All rights reserved.

关键词： POLIOVIRUS   IMMUNOGLOBULINS   VIRAL proteins   ANTIGEN-antibody reactions   CRYSTAL structure   CAPSIDS (Viruses)   ELECTRON microscopy   THREE-dimensional imaging  

摘要： Small, interfacial conformational changes occur in some Ag-Ab interactions. Using cryogenic electron microscopy (cryo-EM), we have demonstrated such changes in a major antigenic site of a poliovirus capsid protein. During cell entry, native human poliovirus (160S particle) converts to a cell entry intermediate (135S particle) and later to an RNA-released (80S) particle. By mixing particles with Fabs of the neutralizing C3 mAb, we labeled the external loop connecting the B and C beta-strands (BC loop) of the capsid protein VP1 (residues 95-105) in the 160S and 135S states. We then determined three-dimensional structures by cryo-EM and enhanced their interpretability by fitting high-resolution coordinates of C3 Fab and the capsid proteins into the density maps. Binding of C3 to either 160S or 135S particles caused residues of the BC loop, located on the tip of a prominent peak known as the "mesa," to move by an estimated 5 angstrom. C3 Abs are neutralizing and can bind bivalently. The orientation of the bound Fabs in our reconstructions suggests that C3 neutralizes poliovirus by binding two adjacent BC loops on the same mesa and inhibiting conformational changes in the viral capsid. The Journal of Immunology, 2013, 191: 884-891.

关键词： clinical study   combination vaccine   DTaP   IPV   Sabin strain  

摘要： Background. Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). Methods. A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Results. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. Conclusions. DTaP-sIPV was shown to be a safe and immunogenic vaccine. Clinical Trials Registration. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study ().

关键词： 脊髓灰质炎病毒   细胞系敏感性实验   质量控制标准株  

摘要： 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2006-2011年所用细胞系对脊灰病毒的敏感性,为维持无脊灰工作提供可靠的质量保证。方法采用96孔微量培养板滴定法测定2006-2011年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。结果河北省脊灰实验室2006-2011年细胞敏感性实验结果:人横纹肌肉瘤细胞(RD)均值及标准差为:Ⅰ型7.66±0.17,Ⅱ型6.31±0.18,Ⅲ型7.18±0.18;转人脊灰病毒受体的小鼠肺细胞系(L20B)细胞均值及标准差为:Ⅰ型6.66±0.20,Ⅱ型6.66±0.19,Ⅲ型6.63±0.10。与河北省脊灰实验室质量控制株(hebei Sabin Master Reference,HBSMR)的参考值相比其滴度均波动在±0.5 log 10 CCID50/0.1 ml以内,结论2006-2011年河北省脊灰实验室所用细胞系对脊灰病毒的敏感性未下降。