Characterization of two engineered dimeric Zika virus envelope proteins as immunogens for neutralizing antibody selection and vaccine design

The Journal of Biological Chemistry
Chunpeng YangRui Gong

Abstract

The envelope protein of Zika virus (ZIKV) exists as a dimer on the mature viral surface and is an attractive antiviral target because it mediates viral entry. However, recombinant soluble wild-type ZIKV envelope (wtZE) might preferentially exist as monomer (monZE). Recently, it has been shown that the A264C substitution could promote formation of dimeric ZIKV envelope protein (ZEA264C), requiring further characterization of purified ZEA264C for its potential applications in vaccine development. We also noted that ZEA264C, connected by disulfide bond, might be different from the noncovalent native envelope dimer on the virion surface. Because the antibody Fc fragment exists as dimer and is widely used for fusion protein construction, here we fused wtZE to human immunoglobulin G1 (IgG1) Fc fragment (ZE-Fc) for noncovalent wtZE dimerization. Using a multistep purification procedure, we separated dimeric ZEA264C and ZE-Fc, revealing that they both exhibit typical β-sheet-rich secondary structures and stabilities similar to those of monZE. The binding activities of monZE, ZEA264C, and ZE-Fc to neutralizing antibodies targeting different epitopes indicated that ZEA264C and ZE-Fc could better mimic the native dimeric status, especiall...Continue Reading

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Related Concepts

Zika virus (organism)
Metazoa
Antibodies, Viral
Antigenic Specificity
Mice, Inbred BALB C
Hybrid Proteins, Recombinant
Corona Virus Membrane Protein E1
Viral Vaccines
Protein Engineering
Protein Conformation, beta-Strand

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