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

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

Cell host & microbe (2020-05-15)
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 Biering, Soila Sukulpolvi-Petty, Guillermina Kuan, Angel Balmaseda, Michael S Diamond, Eva Harris, James E Crowe, Ralph S Baric
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HT Media Supplement (50×) Hybri-Max, lyophilized powder, γ-irradiated, BioXtra, suitable for hybridoma
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, BioReagent, for molecular biology, ≥95%