自然DENV 3感染/疫苗接种后,同种型抗体靶向新的E糖蛋白结构域。

Cell host & microbe Pub Date : 2023-11-08 Epub Date: 2023-10-30 DOI:10.1016/j.chom.2023.10.004
Jennifer E Munt, Sandra Henein, Cameron Adams, Ellen Young, Yixuan J Hou, Helen Conrad, Deanna Zhu, Stephanie Dong, Nurgun Kose, Boyd Yount, Rita M Meganck, Long Ping V Tse, Guillermina Kuan, Angel Balmaseda, Michael J Ricciardi, David I Watkins, James E Crowe, Eva Harris, Aravinda M DeSilva, Ralph S Baric
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引用次数: 0

摘要

包膜(E)糖蛋白是感染四种不同登革热病毒血清型(DENV1-4)中任何一种后的特异性(TS)中和抗体(nAbs)的主要靶标。nAbs可以被诱导到不同的结构E结构域(ED)I、II或III。然而,这些结构域特异性抗体的相对贡献尚不清楚。为了鉴定自然感染或疫苗接种后血清中的主要DENV3-nAb靶点,产生了编码DENV3-EDI、EDII或EDIII的嵌合DENV1重组体。DENV3 EDII是TS多克隆nAb应答的主要靶标,并编码两个或多个中和表位。相反,一些人接种了DENV3单价疫苗,以受试者依赖的方式引发了针对每个ED的血清TS-nAbs,重点是EDI和EDIII。疫苗反应也对DENV3基因型变异敏感。该DENV1/3面板允许测量血清ED TS-nAb,揭示自然感染或接种疫苗后TS-nAbs免疫的差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.

The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.

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