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

Ellen Young, Robert H. Carnahan, Daniela V. Andrade, Nurgun Kose, Rachel S. Nargi, Ethan J. Fritch, Jennifer E. Munt, Michael P. Doyle, Laura White, Thomas J. Baric, Mark Stoops, Aravinda DeSilva, Longping V. Tse, David R. Martinez, Deanna Zhu, Stefan Metz, Marcus P. Wong, Diego A. Espinosa, Magelda Montoya, Scott B. BieringSoila Sukulpolvi-Petty, Guillermina Kuan, Angel Balmaseda, Michael S. Diamond, Eva Harris, James E. Crowe, Ralph S. Baric

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Pages (from-to)710-724.e7
JournalCell Host and Microbe
Volume27
Issue number5
DOIs
StatePublished - May 13 2020

Keywords

  • DENV3
  • antigenic site
  • chimeric virus
  • dengue virus serotype 3
  • envelope protein
  • flavivirus
  • functional epitopes
  • in vivo protection
  • neutralizing monoclonal antibodies

Fingerprint

Dive into the research topics of 'Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies'. Together they form a unique fingerprint.

Cite this