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Zika virus is a type of mosquito-borne pathogen.
On July 15, 2021, Gao Fu, Dai Lianpan, Yan Jinghua, etc.
The Zika/Dengue virus cross-antibodies that cause the ADE effect mainly target the conserved region of the fusion peptide (FL) of the viral surface structural protein prM and E protein (Science 328, 745–748 (2010))
The team of Academician Gao Fu has been conducting research on Zika virus since 2016, and resolved the crystal structure of the protective immunogen E protein of Zika virus, and isolated a series of neutralizing/protecting antibodies targeting different domains of the E protein , Resolved the structural basis of representative ADE antibodies targeting FL epitopes (Cell Host Microbe 19, 696–704 (2016); Sci.
In this study, the researchers adopted a reverse vaccinology strategy that uses antibodies to guide vaccine design
The results showed that a single immunization with the MutB/C vaccine can produce a clear immune response, which completely protects the mice against the Zika virus challenge, and the viral load is undetectable in all target tissues infected by the virus
The researchers further verified the ADE of MutB/C against dengue virus infection through in vitro and in vivo experiments
In order to further explore the immunological basis of the modified vaccine MutB/C to eliminate ADE, the researchers analyzed the characteristics of antigen-specific BCR in the lymph nodes of the immunized mice through the B-cell receptor (BCR) single-cell sequencing method
The researchers finally analyzed the molecular basis of one of the antigen-modified E protein MutC binding neutralizing antibodies, and found that MutC can still maintain the dimer structure of E protein through new forces, which is very important for activating effective neutralizing antibodies
The study successfully applied structural guidance antigen design to solve the problem of Zika vaccine ADE, and provided a beautiful solution to the long-standing problems in the development of Zika vaccine
Academician Gao Fu, researcher Dai Lianpan, and researcher Yan Jinghua of the Institute of Microbiology, Chinese Academy of Sciences are the co-corresponding authors of the paper
