Drexler Jan Felix, Grard Gilda, Lukashev Alexander N, Kozlovskaya Liubov I, Böttcher Sindy, Uslu Gökhan, Reimerink Johan, Gmyl Anatoly P, Taty-Taty Raphaël, Lekana-Douki Sonia Etenna, Nkoghe Dieudonné, Eis-Hübinger Anna M, Diedrich Sabine, Koopmans Marion, Leroy Eric M, Drosten Christian
Institute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany;
Centre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12889-94. doi: 10.1073/pnas.1323502111. Epub 2014 Aug 18.
In 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 analysis 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.
2010年，刚果共和国黑角市发生了大规模脊髓灰质炎疫情，致死率高达47%，情况异常。疫苗介导的针对此次疫情病毒的免疫力从未得到过研究。从一例致死病例中分离出的一株野生脊髓灰质炎病毒1型（WPV1，称为PV1-RC2010）在关键抗原位点2（AgS2，衣壳蛋白VP1的221位氨基酸序列从SAAL变为PADL）呈现出一种前所未知的氨基酸交换组合。在另外11株来自致死病例的WPV1毒株中也检测到了这些交换。PV1-RC2010能够逃避与AgS2相关的三种不同单克隆抗体的中和作用。在来自致死病例（在补充免疫前死亡，n = 24）、近期口服脊髓灰质炎疫苗的加蓬接种者（n = 12）、常规接种疫苗的德国医学生（n = 34）以及接受抗脊髓灰质炎病毒免疫力检测的德国门诊患者（n = 17）的血清中，在Vero细胞、人横纹肌肉瘤细胞和人表皮样癌2细胞上测试了病毒中和情况。致死性脊髓灰质炎病例提供了先前接种三价疫苗的实验室证据。针对PV1-RC2010的中和抗体滴度显著低于针对疫苗株Sabin-1、1965年和2010年分离出的两株基因不同的WPV1以及两株基因不同的疫苗衍生PV株的中和抗体滴度。按照世界卫生组织方案检测的德国疫苗接种者中，15% - 29%根据其中和滴度（血清稀释度<1:8）未得到保护，尽管所有人对Sabin-1都有免疫力。对WPV1疫情毒株的系统发育分析表明，病毒祖先近期从亚洲传入，形成了独立的安哥拉和刚果谱系。只有后者携带这两个关键的AgS2突变。在以疫苗衍生免疫力为主的人群中，抗原变异的PVs可能在脊髓灰质炎根除的最后阶段变得至关重要。持续的疫苗接种覆盖率以及临床和环境监测将是必要的。
