[帖帖不休之发帖神器未注册作者扣扣:659895301]疫苗 ? 进展 市场 政策 人物 公司 会议 首页 ? 疫苗 ? PNAS：变异病毒或可破坏疫苗的作用 PNAS：变异病毒或可破坏疫苗的作用 来源：生物谷 2014-08-24 13:21 2014年8月24日 讯 /生物谷BIOON/ --由于有效的疫苗接种，脊髓灰质炎被认为是几乎已经根除。全世界每年只有几百人患病。然而，波恩大学的科学家与来自加蓬的同事一起发现了一个令人震惊的事实：2010年在刚果爆发的受害者体内发现变异病毒能够在相当大的程度上抵抗疫苗的保护。在德国病原体也可能感染了许多人。2010年在刚果脊髓灰质炎爆发流行特别严重。445人被证实已经感染，而且大多数都是年轻人，已感染此病的209人性命堪忧，这种高死亡率非常令人震惊。同样一项重要的事实是，许多受到影响的人是接种过疫苗的人：调查表明，一半的患者有接种过规定的三次疫苗的接种剂量。迄今为止疫苗接种已被认为是一种非常有效的抵抗小儿麻痹症的方法。“我们从死者身上分离出脊灰病毒，”Jan Felix Drexler博士解释道，“病原体携带突变体在决定性的点改变其构成。”结果：通过接种疫苗得到的抗体诱导几乎不可能阻止病毒变异并在机体内认为变异病毒无害。研究人员检测了为何新病原体能够成功逃避免疫系统监视。为了这个目的，研究人员测试了34个波恩大学医学院学生的血样，他们都是在童年时期接种过脊髓灰质炎疫苗。初步测试显示：测试中血液中的抗体没有问题，包括“正常”的脊髓灰质炎病毒。但是变异病毒的情况不同，相比较之下免疫反应较弱得多。“我们估计，五分之一的波恩受试者可以通过新的脊髓灰质炎病毒受感染，甚至三分之一会被感染。”Drosten教授说。世界卫生组织(世卫组织)已承诺在未来几年的目标中根除脊髓灰质炎病毒。天花就是成功的例子，由于疫苗接种策略一致，全球自1980年天花就被列为免费接种。类似的事情可以再次成功：脊髓灰质炎病毒也只能在人与人之间传播。它不会通过动物病原体及水疫源等传染源传染到人体，而这些传染源会导致疾病的反复及蔓延。与天花类似、脊髓灰质炎疫苗会对机体提供特殊保护。然而，这种情况下当病毒发生变异时却不适用。“当这样一个变异病原体遇到没有足够持续接种疫苗的人群时，那么事情变得非常危险，”科学家们警告说。由于大规模的疫苗接种计划和卫生措施的执行使得刚果的脊髓灰质炎流行已经被有效控制了。现有疫苗甚至因此似乎足以迅速而稳定的有效控制脊灰病毒，但新的病原体仍然是一个警告：“我们不能坐下来什么也不做，”科学家们警告道“我们需要进一步提高疫苗的接种率并开发新的、更有效的疫苗。只有这样做我们的才有机会永久的消灭小儿麻痹症。”（yuyu学院）doi:10.1073/pnas.1323502111PMC:PMID:Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010Jan Felix Drexlera,1, Gilda Grardb,1, Alexander N. Lukashevc, Liubov I. Kozlovskayac, Sindy B?ttcherd, G?khan Uslue, Johan Reimerinke, Anatoly P. Gmylc,f, Rapha?l Taty-Tatyg, Sonia Etenna Lekana-Doukib, Dieudonné Nkogheb, Anna M. Eis-Hübingera, Sabine Diedrichd, Marion Koopmanse, Eric M. Leroyb,h,1,2, and Christian Drostena,1,2In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15–29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic ysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.
