共 50 条
Structures of the Varicella Zoster Virus Glycoprotein E and Epitope Mapping of Vaccine-Elicited Antibodies
被引:0
|作者:
Harshbarger, Wayne D.
[1
]
Holzapfel, Genevieve
[1
]
Seraj, Nishat
[1
]
Tian, Sai
[1
]
Chesterman, Chelsy
[1
]
Fu, Zongming
[1
]
Pan, Yan
[1
]
Harelson, Claire
[1
]
Peng, Dongjun
[1
]
Huang, Ying
[1
,2
]
Chandramouli, Sumana
[1
,3
]
Malito, Enrico
[1
,4
]
Bottomley, Matthew James
[1
,5
]
Williams, James
[1
]
机构:
[1] GSK, Rockville, MD 20850 USA
[2] WuXi Biol, Cranbury, NJ 08512 USA
[3] Moderna Therapeut Inc, Cambridge, MA 02142 USA
[4] Schrodinger Inc, New York, NY 10036 USA
[5] Dynavax Technol Corp, Emeryville, CA 94608 USA
来源:
关键词:
vaccines;
herpes zoster;
antibodies;
pathogen-host interaction;
HERPES-ZOSTER;
SUBUNIT VACCINE;
EFFICACY;
GE;
PHOSPHORYLATION;
REPLICATION;
INFECTION;
SHINGLES;
FUSION;
SAFETY;
D O I:
10.3390/vaccines12101111
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Background: 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, AS01B-adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. Objectives: We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. Methods: 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. Results: 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. Conclusions: 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. Teaser: Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies.
引用
收藏
页数:18
相关论文