Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010
Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010
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DOI：
10.1073/pnas.1323502111
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发表时间：
2014-09-02
影响因子：
11.1
通讯作者：
Drosten, Christian
中科院分区：
文献类型：
--
作者：
Drexler, Jan Felix;Grard, Gilda;Drosten, Christian
2010年，刚果共和国黑角发生了一次大规模脊髓灰质炎疫情，致死率高达47%。从未研究过疫苗介导的抗暴发病毒免疫。从致死病例中分离的野生型脊髓灰质炎病毒1（WPV 1）（称为PV 1-RC 2010）在关键抗原位点2（AgS 2，VP 1衣壳蛋白位置（221）萨尔->（221）PADL）显示出先前未知的氨基酸交换组合。在来自致死性病例的另外11株WPV 1菌株中也检测到这些交换。PV 1-RC 2010逃脱了与AgS 2相关的三种不同mAb的中和。在补充免疫前死亡的致命病例（n = 24）、最近口服脊髓灰质炎疫苗接种的加蓬接受者（n = 12）、常规接种疫苗的德国医学生（n = 34）和使用Vero、人横纹肌肉瘤和人表皮样癌2细胞进行抗脊髓灰质炎病毒免疫试验的德国门诊患者（n = 17）的血清中检测病毒中和作用。致死性脊髓灰质炎病例提供了既往三价疫苗接种的实验室证据。针对PV 1-RC 2010的中和抗体滴度显著低于针对疫苗株Sabin-1的中和抗体滴度，Sabin-1是1965年和2010年分离的两种遗传上不同的WPV 1，以及两种遗传上不同的疫苗衍生PV株。在根据世界卫生组织方案进行检测的德国疫苗接种者中，根据其中和滴度，15-29%的人没有受到保护（
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 (221)SAAL ->(221)PADL). 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 anti-poliovirus 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 (