8V5P

Crystal Structure of the C-terminal domain of the VZV gE ectodomain in complex with the Fab of human antibody 5A2

Summary for 8V5P

• Entry DOI: 10.2210/pdb8v5p/pdb
• Descriptor: Envelope glycoprotein E, 5A2 Fab heavy chain, 5A2 Fab Light Chain (3 entities in total)
• Functional Keywords: glycoprotein e, varicella, zoster, herpes, virus, antibody, viral protein
• Biological source: Human alphaherpesvirus 3 (Varicella-zoster virus); More
• Total number of polymer chains: 12
• Total formula weight: 306095.55

Authors

Harshbarger, W.,Malito, E. (deposition date: 2023-11-30, release date: 2024-10-09, Last modification date: 2024-11-13)

Primary citation

Harshbarger, W.D.,Holzapfel, G.,Seraj, N.,Tian, S.,Chesterman, C.,Fu, Z.,Pan, Y.,Harelson, C.,Peng, D.,Huang, Y.,Chandramouli, S.,Malito, E.,Bottomley, M.J.,Williams, J.
Structures of the Varicella Zoster Virus Glycoprotein E and Epitope Mapping of Vaccine-Elicited Antibodies.
Vaccines (Basel), 12:-, 2024

PubMed Abstract: Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for anti-VZV antibodies. Importantly, gE is the sole antigen in Shingrix, a highly efficacious, AS01-adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. : We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. : We used X-ray crystallography and cryo-electron microscopy to elucidate structures of gE bound by recombinant Fabs of antibodies previously elicited through vaccination with Zostavax, a live, attenuated vaccine. : The 3D structures resolve distinct central and C-terminal antigenic domains, presenting an array of diverse conformational epitopes. The central domain has two beta-sheets and two alpha helices, including an IgG-like fold. The C-terminal domain exhibits 3 beta-sheets and an Ig-like fold and high structural similarity to HSV1 gE. : gE from VZV-infected cells elicits a human antibody response with a preference for the gI binding domain of gE. These results yield insights to VZV gE structure and immunogenicity, provide a framework for future studies, and may guide the design of additional herpesvirus vaccine antigens. Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies.

PubMed: 39460278
DOI: 10.3390/vaccines12101111

Experimental method

X-RAY DIFFRACTION (4.33 Å)