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本文引用的文献

1
Tracking the polyclonal neutralizing antibody response to a dengue virus serotype 1 type-specific epitope across two populations in Asia and the Americas.追踪亚洲和美洲两个人群中针对登革热病毒血清型 1 型特异性表位的多克隆中和抗体反应。
Sci Rep. 2019 Nov 7;9(1):16258. doi: 10.1038/s41598-019-52511-z.
2
Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents.四价登革热疫苗在健康儿童和青少年中的功效。
N Engl J Med. 2019 Nov 21;381(21):2009-2019. doi: 10.1056/NEJMoa1903869. Epub 2019 Nov 6.
3
Beyond Neutralizing Antibody Levels: The Epitope Specificity of Antibodies Induced by National Institutes of Health Monovalent Dengue Virus Vaccines.超越中和抗体水平：美国国立卫生研究院单价登革病毒疫苗诱导的抗体的表位特异性。
J Infect Dis. 2019 Jun 19;220(2):219-227. doi: 10.1093/infdis/jiz109.
4
Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient.预先存在的登革热免疫力导致 Zika 病毒感染患者中偏向 DENV 的浆母细胞反应。
Viruses. 2018 Dec 29;11(1):19. doi: 10.3390/v11010019.
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Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization.登革病毒 4 型毒株之间的遗传变异影响人体抗体结合和中和作用。
Cell Rep. 2018 Oct 30;25(5):1214-1224. doi: 10.1016/j.celrep.2018.10.006.
6
Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement.抗原特异性抗体 Fc 糖基化通过募集补体增强体液免疫。
Sci Immunol. 2018 Aug 17;3(26). doi: 10.1126/sciimmunol.aat7796.
7
Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy.登革热血清阳性状态对登革热疫苗安全性和有效性的影响。
N Engl J Med. 2018 Jul 26;379(4):327-340. doi: 10.1056/NEJMoa1800820. Epub 2018 Jun 13.
8
The Molecular Specificity of the Human Antibody Response to Dengue Virus Infections.人类对登革热病毒感染的抗体反应的分子特异性。
Adv Exp Med Biol. 2018;1062:63-76. doi: 10.1007/978-981-10-8727-1_5.
9
Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate.分析人体血清对一种活的减毒四价登革热候选疫苗的抗体反应。
J Infect Dis. 2018 May 25;217(12):1932-1941. doi: 10.1093/infdis/jiy063.
10
Reconstruction of antibody dynamics and infection histories to evaluate dengue risk.重建抗体动态和感染史以评估登革热风险。
Nature. 2018 May;557(7707):719-723. doi: 10.1038/s41586-018-0157-4. Epub 2018 May 23.

鉴定登革病毒 3 型特异性抗原表位，这些表位是中和性人抗体的作用靶点。

Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies.

机构信息

Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, USA.

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.

出版信息

Cell Host Microbe. 2020 May 13;27(5):710-724.e7. doi: 10.1016/j.chom.2020.04.007.

DOI:10.1016/j.chom.2020.04.007
PMID:32407709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7309352/
Abstract

The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of Nicaragua and isolated 15 DENV3 TS mAbs recognizing the envelope (E) glycoprotein. Functional epitope mapping of these mAbs and small animal prophylaxis studies revealed a complex landscape with protective epitopes clustering in at least 6-7 antigenic sites. Potently neutralizing TS mAbs recognized sites principally in E glycoprotein domains I and II, and patterns suggest frequent recognition of quaternary structures on the surface of viral particles.

摘要

登革热病毒（DENV）疫苗的合理设计需要深入了解抗体介导免疫的分子基础。初次感染后，针对 DENV 的持久保护性抗体反应是血清型特异性的。然而，对于 DENV 型特异性（TS）抗体的抗原决定簇，特别是对于 DENV 血清型 3，人们的理解并不完全，因为只有一种研究充分、具有强中和作用的人源单克隆抗体（mAb）。在这里，我们研究了尼加拉瓜流行地区自然感染 DENV 的儿童的人类 B 细胞反应，并分离出 15 种针对包膜（E）糖蛋白的 DENV3 TS mAb。这些 mAb 的功能表位作图和小动物预防研究揭示了一个复杂的景观，保护性表位聚集在至少 6-7 个抗原位点上。具有强大中和作用的 TS mAb 识别的主要是 E 糖蛋白结构域 I 和 II 的表位，且这些模式表明经常识别病毒颗粒表面的四级结构。