Publication Date:
2015-07-04
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672004/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672004/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fibriansah, Guntur -- Ibarra, Kristie D -- Ng, Thiam-Seng -- Smith, Scott A -- Tan, Joanne L -- Lim, Xin-Ni -- Ooi, Justin S G -- Kostyuchenko, Victor A -- Wang, Jiaqi -- de Silva, Aravinda M -- Harris, Eva -- Crowe, James E Jr -- Lok, Shee-Mei -- K08 AI103038/AI/NIAID NIH HHS/ -- R01 AI107731/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI065359/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):88-91. doi: 10.1126/science.aaa8651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore. ; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA. ; Department of Medicine, Vanderbilt University, Nashville, TN, USA. The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. ; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. ; The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138979" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Monoclonal/*ultrastructure
;
Antibodies, Neutralizing/*ultrastructure
;
Coinfection/immunology
;
Cross Reactions
;
Cryoelectron Microscopy
;
Dengue Virus/*immunology
;
Disease Models, Animal
;
Epitopes/immunology
;
Humans
;
Mice
;
Serogroup
;
Viral Envelope Proteins/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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