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[EID Virtual Seminar] - STRUCTURE BASED DEVELOPMENT OF DENGUE VACCINE
Abstract:
We determined the crystal structure of a potent neutralizing antibody ZK2B10 in complex with DIII of the ZIKV E protein and revealed the epitope on the lateral ridge of DIII. Cryo-EM structure of ZK2B10 in complex with mature ZIKV showed that the antibody binds DIIIs around the icosahedral
2-fold, 3-fold, and in addition, the 5-fold axes, a distinct feature compared to those reported
DIII-specific antibodies. The binding of ZK2B10 to ZIKV has no detectable effect on viral attachment to target cells or on conformational changes of the E glycoprotein in the acidic environment, suggesting that ZK2B10 functions at steps between the formation of the fusion intermediate and membrane fusion. The results suggest that the DIII pentamers around the 5 fold vertexes may be used as an antigen for the development of subunit vaccine against ZIKV or Dengue virus. DIIIs of Dengue virus attached to a virus like scaffold induced strong immune responses in mice, providing a possible alternative way for the design of vaccine antigens.
Date and Time
02 Jul 2021 @ 16:00 - 02 Jul 2021 @ 17:00
Speaker
Ye Xiang received his bachelor’s degree from the College of Chemistry and Molecular Engineering at Peking University in 1998 and his doctorate from the Institute of Biophysics at the Chinese Academy of Sciences (CAS) in 2003. He pursued his postdoctoral training in the laboratory of Michael G. Rossmann at Purdue University, Indiana, between 2005 and 2012, where he studied the molecular mechanisms involved in the infection and assembly of bacteriophage ф29. In 2012, Dr. Xiang obtained funding support from the government of China. In 2013, he returned to Tsinghua University in Beijing as an assistant professor to initiate his independent research. He was promoted to the position of a tenured associate professor by the end of 2017. The
long-term goal of Dr. Xiang's group is to understand the molecular mechanisms underlying virus assembly and infection, and perform structure directed vaccine development. The group mainly uses biochemical and biophysical approaches for their studies. To date, the Xiang group has published more 20 scientific articles in the related field.