Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies.,Cell Host & Microbe

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Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-05-13 , DOI: 10.1016/j.chom.2020.04.007
Ellen Young ₁ , Robert H Carnahan ₂ , Daniela V Andrade ₃ , Nurgun Kose ₄ , Rachel S Nargi ₄ , Ethan J Fritch ₅ , Jennifer E Munt ₁ , Michael P Doyle ₆ , Laura White ₅ , Thomas J Baric ₁ , Mark Stoops ₅ , Aravinda DeSilva ₅ , Longping V Tse ₁ , David R Martinez ₁ , Deanna Zhu ₁ , Stefan Metz ₅ , Marcus P Wong ₃ , Diego A Espinosa ₃ , Magelda Montoya ₃ , Scott B Biering ₃ , Soila Sukulpolvi-Petty ₇ , Guillermina Kuan ₈ , Angel Balmaseda ₉ , Michael S Diamond ₁₀ , Eva Harris ₃ , James E Crowe ₁₁ , Ralph S Baric ₁₂

Affiliation

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.
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Health Center Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua.
National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua.
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.

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.

中文翻译：

登革热病毒血清型 3 特定抗原位点的鉴定是中和人类抗体的目标。

登革热病毒 (DENV) 疫苗的合理设计需要详细了解抗体介导免疫的分子基础。初次感染后对 DENV 的持久保护性抗体反应是血清型特异性的。然而，对 DENV 类型特异性 (TS) 抗体的抗原决定簇的了解还不完全，尤其是 DENV 血清型 3，它只有一种经过充分研究的强中和人单克隆抗体 (mAb)。在这里，我们研究了尼加拉瓜流行地区自然感染 DENV 后儿童的人类 B 细胞反应，并分离出 15 种识别包膜 (E) 糖蛋白的 DENV3 TS mAb。这些 mAb 的功能性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。

更新日期：2020-05-13

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