A Chimeric Zika Virus between Viral Strains MR766 and BeH819015 Highlights a Role for E-glycan Loop in Antibody-mediated Virus Neutralization
A Chimeric Zika Virus between Viral Strains MR766 and BeH819015 Highlights a Role for E-glycan Loop in Antibody-mediated Virus Neutralization
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DOI：
10.3390/vaccines7020055
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发表时间：
2019-06-01
期刊：
影响因子：
7.8
通讯作者：
Despres, Philippe
中科院分区：
文献类型：
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作者：
Frumence, Etienne;Viranaicken, Wildriss;Despres, Philippe
寨卡病毒（ZIKV）是一种新出现的蚊媒黄病毒，是主要的公共卫生问题。ZIKV感染被认为是先天性Zika疾病和其他神经缺陷的原因，没有特定的预防或治疗方法。由于体液免疫应答是保护性免疫的重要组成部分，因此迫切需要赋予针对ZIKV感染的保护的有效疫苗。在本研究中，我们评估了嵌合病毒克隆ZIKBeHMR-2的免疫原性，其中非洲毒株MR 766骨架的结构蛋白编码区被流行毒株BeH 819015的对应物取代。在E蛋白（E-GL）的聚糖环中引入三个氨基酸取代I152 T、T156 I和H158 Y，使ZIKBeHMR-2成为非糖基化病毒。腹膜内接种ZIKBeHMR-2的成年BALB/c小鼠产生了针对病毒蛋白E和NS 1的抗ZIKV抗体，加强剂量增加了抗体滴度。用ZIKBeHMR-2免疫导致中和抗ZIKV抗体的快速产生。抗体介导的ZIKV中和针对病毒株MR 766是有效的，而流行性ZIKV株对抗ZIKBeHMR-2免疫血清的中和敏感性差。从我们的数据，我们提出位置E-152、E-156和E-158处的三个E-GL残基极大地影响ZIKV上的中和抗体表位的可及性。
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which is of major public health concern. ZIKV infection is recognized as the cause of congenital Zika disease and other neurological defects, with no specific prophylactic or therapeutic treatments. As the humoral immune response is an essential component of protective immunity, there is an urgent need for effective vaccines that confer protection against ZIKV infection. In the present study, we evaluate the immunogenicity of chimeric viral clone ZIKBeHMR-2, in which the region encoding the structural proteins of the African strain MR766 backbone was replaced with its counterpart from the epidemic strain BeH819015. Three amino-acid substitutions I152T, T156I, and H158Y were introduced in the glycan loop of the E protein (E-GL) making ZIKBeHMR-2 a non-glycosylated virus. Adult BALB/c mice inoculated intraperitoneally with ZIKBeHMR-2 developed anti-ZIKV antibodies directed against viral proteins E and NS1 and a booster dose increased antibody titers. Immunization with ZIKBeHMR-2 resulted in a rapid production of neutralizing anti-ZIKV antibodies. Antibody-mediated ZIKV neutralization was effective against viral strain MR766, whereas epidemic ZIKV strains were poorly sensitive to neutralization by anti-ZIKBeHMR-2 immune sera. From our data, we propose that the three E-GL residues at positions E-152, E-156, and E-158 greatly influence the accessibility of neutralizing antibody epitopes on ZIKV.