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TitleA pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.
Journal, issue, pagesEmerg Microbes Infect, Vol. 13, Issue 1, Page 2432366, Year 2024
Publish dateNov 25, 2024
AuthorsPengfei Fan / Bingjie Sun / Zixuan Liu / Ting Fang / Yi Ren / Xiaofan Zhao / Zhenwei Song / Yilong Yang / Jianmin Li / Changming Yu / Wei Chen /
PubMed Abstract is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross- ... is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species. The cryo-electron microscopy structure of 2G1 Fab in complex with the GPΔMucin trimer reveals that 2G1 binds a quaternary pocket formed by three subunits from two GP protomers. 2G1 recognizes highly conserved epitopes among filoviruses and achieves neutralization by blocking GP proteolysis. We designed an efficient mRNA module capable of producing test antibodies at expression levels exceeding 1500 ng/mL in vitro. The lipid nanoparticle (LNP)-encapsulated mRNA-2G1 exhibited potent neutralizing activities against the HIV-pseudotyped Ebola and Sudan viruses that were 19.8 and 12.5 times that of IgG format, respectively. In mice, the antibodies encoded by the mRNA-2G1-LNP peaked within 24 h, effectively blocking the invasion of pseudoviruses with no apparent liver toxicity. This study suggests that the 2G1 antibody and its mRNA formulation represent promising candidate interventions for orthoebolavirus disease, and it provides an efficient mRNA framework applicable to antibody-based therapies.
External linksEmerg Microbes Infect / PubMed:39560055 / PubMed Central
MethodsEM (single particle)
Resolution2.98 Å
Structure data

EMDB-38899, PDB-8y3u:
Ebola virus glycoprotein in complex with a broadly neutralizing antibody 2G1
Method: EM (single particle) / Resolution: 2.98 Å

Source
  • Henipavirus nipahense
  • ebola virus
  • homo sapiens (human)
KeywordsANTIVIRAL PROTEIN

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