| Literature DB >> 32407709 |
Ellen Young1, Robert H Carnahan2, Daniela V Andrade3, Nurgun Kose4, Rachel S Nargi4, Ethan J Fritch5, Jennifer E Munt1, Michael P Doyle6, Laura White5, Thomas J Baric1, Mark Stoops5, Aravinda DeSilva5, Longping V Tse1, David R Martinez1, Deanna Zhu1, Stefan Metz5, Marcus P Wong3, Diego A Espinosa3, Magelda Montoya3, Scott B Biering3, Soila Sukulpolvi-Petty7, Guillermina Kuan8, Angel Balmaseda9, Michael S Diamond10, Eva Harris11, James E Crowe12, Ralph S Baric13.
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.Entities:
Keywords: DENV3; antigenic site; chimeric virus; dengue virus serotype 3; envelope protein; flavivirus; functional epitopes; in vivo protection; neutralizing monoclonal antibodies
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Year: 2020 PMID： 32407709 PMCID： PMC7309352 DOI： 10.1016/j.chom.2020.04.007
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023