Journal
SCIENCE
Volume 349, Issue 6243, Pages 88-91Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaa8651
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Funding
- Ministry of Education Tier 3 [R-913-301-146-112]
- U.S. NIH [U54 AI057157]
- NIH (National Institute of Allergy and Infectious Diseases) [R01 AI107731]
- NIH [K08 AI103038, U54 AI065359]
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There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 locks two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.
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