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Zika virus is a type of mosquito-borne pathogen.
2021 Nian 7 Yue 15 days, Institute of Microbiology, Chinese Academy of Sciences high-fu, even wearing climbing, Yan Jinghua, etc.
The Zika / Dengue virus cross-antibody that causes the ADE effect mainly targets 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
Figure 1.
The results showed that, MUTB / C vaccine immunization can generate an immune response of clearing , completely protected mice against challenge Zika virus , in all target tissues are infected with the virus undetectable viral load
The researchers further verified the ADE of MutB/C against dengue virus infection through in vitro and in vivo experiments .
Figure 3.
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 .
Figure 4.
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
