Identification of linear B-cell epitopes on the gE envelope protein of varicella-zoster virus

Varicella-zoster virus (VZV) is a highly infectious DNA virus with an envelope. It is the pathogen causing varicella and herpes zoster. The glycoprotein E (gE) envelope protein, a primary target for VZV diagnostic reagents and vaccines, is highly immunogenic and plays a critical role in the pathogenicity of VZV. However, the B-cell epitopes and immunodominant regions of gE remain poorly characterized. In this study, we utilized anti-VZV gE monoclonal antibodies to localize antigenic sequences of gE at 101 VYNQGRGIDSGERLMQPTQM 120 , 124 EDLGDDTGIHVI 135 , and 141 DDRHKIVNVDQRQYGDVFKGD 161 by the overlapping peptide method. Results from conservative and structural analysis revealed that 101 VYNQGRGIDSGERLMQPTQM 120 was a highly conserved epitope and exposed on the surface of VZV gE. These findings provide important information for researching the VZV diagnostic reagents and may facilitate further efforts to design VZV vaccines. IMPORTANCE VZV infection can cause varicella (commonly in children) and herpes zoster (in adults). Currently, the prevention of VZV primarily relies on vaccination. The currently approved vaccines to prevent varicella are live-attenuated viruses that carry the risk of inducing herpes zoster. Therefore, there is an urgent need to develop safer novel VZV vaccines. The gE protein, the most abundant and highly conserved glycoprotein on the VZV envelope, exhibits strong immunogenicity and can induce neutralizing antibodies, making it a critical target for developing novel VZV vaccines and diagnostic reagents. To date, research on the B-cell epitopes of the VZV gE protein remains limited, particularly regarding the identification of conformational B-cell epitopes. This project aims to identify linear B-cell epitopes of the gE protein, providing a scientific foundation for the development of novel VZV vaccines based on epitopes.