Investigation of the immunogenicity of Zika glycan loop

Virology Journal

Anh-Viet Nguyen¹  Annie Elong Ngono¹  Sujan Shresta¹  Luisa W. Cheng²  Christina C. Tam²  Mikhail Martchenko Shilman³  Elizabeth A. Henderson³  Laurence K. Grill³  Matt McGee⁴  Hal Padgett⁴ 

[1] Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology;Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, United States Department of Agriculture (USDA);Henry E. Riggs School of Applied Life Sciences, Keck Graduate Institute;Novici Biotech LLC;

关键词: Zika;    Envelope;    Glycan loop;    Neutralizing antibodies;   

DOI  :  10.1186/s12985-020-01313-1

来源: DOAJ

【 摘 要 】

Abstract Background Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus. Previous studies have identified neutralizing antibodies from Zika patients that bind to quaternary epitopes across neighboring envelope (E) proteins, called E dimer epitopes (EDE). An asparagine-linked glycan on the “glycan loop” (GL) of the ZIKV envelope protein protects the functionally important “fusion loop” on the opposite E subunit in the dimer, and EDE antibodies have been shown to bind to both of these loops. Human EDE antibodies have been divided into two subclasses based on how they bind to the glycan loop region: EDE1 antibodies do not require glycosylation for binding, while EDE2 antibodies strongly rely on the glycan for binding. Methods ZIKV GL was expressed on tobacco mosaic virus nanoparticles. Mice were immunized with GL or full-length monomeric E and the immune response was analyzed by testing the ability of sera and monoclonal antibodies to bind to GL and to neutralize ZIKV in in vitro cellular assay. Results We report here the existence of ZIKV moderately neutralizing antibodies that bind to E monomers through epitopes that include the glycan loop. We show that sera from human Zika patients contain antibodies capable of binding to the unglycosylated glycan loop in the absence of the rest of the envelope protein. Furthermore, mice were inoculated with recombinant E monomers and produced neutralizing antibodies that either recognize unglycosylated glycan loop or require glycan for their binding to monomeric E. We demonstrate that both types of antibodies neutralize ZIKV to some extent in a cellular virus neutralization assay. Conclusions Analogous to the existing EDE antibody nomenclature, we propose a new classification for antibodies that bind to E monomer epitopes (EME): EME1 and EME2 for those that do not require and those that do require glycan for binding to E, respectively.

【 授权许可】

Unknown