Download MendeleyNon-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection.
Hong, J., Zhong, L., Liu, L., Wu, Q., Zhang, W., Chen, K., Wei, D., Sun, H., Zhou, X., Zhang, X., Kang, Y.F., Huang, Y., Chen, J., Wang, G., Zhou, Y., Chen, Y., Feng, Q.S., Yu, H., Li, S., Zeng, M.S., Zeng, Y.X., Xu, M., Zheng, Q., Chen, Y., Zhang, X., Xia, N.(2023) Cell Rep Med 4: 101296-101296
- PubMed: 37992686
- DOI: https://doi.org/10.1016/j.xcrm.2023.101296
- Primary Citation of Related Structures:
7YOY, 7YP1, 7YP2 - PubMed Abstract:
Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection.
Organizational Affiliation:
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Collaborative Innovation Center of Biologic Products, National Innovation Platform for Industry-Education Integration in Vaccine Research, Research Unit of Frontier Technology of Structural Vaccinology of the Chinese Academy of Medical Sciences, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361005, China; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
