PMID- 26189681
OWN - NLM
STAT- MEDLINE
DCOM- 20151028
LR  - 20181113
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 162
IP  - 3
DP  - 2015 Jul 30
TI  - Structure-Guided Design of an Anti-dengue Antibody Directed to a 
      Non-immunodominant Epitope.
PG  - 493-504
LID - S0092-8674(15)00827-2 [pii]
LID - 10.1016/j.cell.2015.06.057 [doi]
AB  - Dengue is the most common vector-borne viral disease, causing nearly 400 million 
      infections yearly. Currently there are no approved therapies. Antibody epitopes 
      that elicit weak humoral responses may not be accessible by conventional B cell 
      panning methods. To demonstrate an alternative strategy to generating a 
      therapeutic antibody, we employed a non-immunodominant, but functionally 
      relevant, epitope in domain III of the E protein, and engineered by 
      structure-guided methods an antibody directed to it. The resulting antibody, 
      Ab513, exhibits high-affinity binding to, and broadly neutralizes, multiple 
      genotypes within all four serotypes. To assess therapeutic relevance of Ab513, 
      activity against important human clinical features of dengue was investigated. 
      Ab513 mitigates thrombocytopenia in a humanized mouse model, resolves vascular 
      leakage, reduces viremia to nearly undetectable levels, and protects mice in a 
      maternal transfer model of lethal antibody-mediated enhancement. The results 
      demonstrate that Ab513 may reduce the public health burden from dengue.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Robinson, Luke N
AU  - Robinson LN
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA; 
      Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA.
FAU - Tharakaraman, Kannan
AU  - Tharakaraman K
AD  - Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA.
FAU - Rowley, Kirk J
AU  - Rowley KJ
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Costa, Vivian V
AU  - Costa VV
AD  - Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for 
      Research and Technology, Singapore.
FAU - Chan, Kuan Rong
AU  - Chan KR
AD  - Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 
      College Road, Singapore 169857.
FAU - Wong, Yee Hwa
AU  - Wong YH
AD  - School of Biological Sciences, Nanyang Technological University, 60 Nanyang 
      Drive, Singapore 637551.
FAU - Ong, Li Ching
AU  - Ong LC
AD  - Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for 
      Research and Technology, Singapore.
FAU - Tan, Hwee Cheng
AU  - Tan HC
AD  - Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 
      College Road, Singapore 169857.
FAU - Koch, Tyree
AU  - Koch T
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Cain, David
AU  - Cain D
AD  - Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA.
FAU - Kirloskar, Rama
AU  - Kirloskar R
AD  - Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA.
FAU - Viswanathan, Karthik
AU  - Viswanathan K
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Liew, Chong Wai
AU  - Liew CW
AD  - School of Biological Sciences, Nanyang Technological University, 60 Nanyang 
      Drive, Singapore 637551.
FAU - Tissire, Hamid
AU  - Tissire H
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Ramakrishnan, Boopathy
AU  - Ramakrishnan B
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Myette, James R
AU  - Myette JR
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Babcock, Gregory J
AU  - Babcock GJ
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Sasisekharan, V
AU  - Sasisekharan V
AD  - Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA.
FAU - Alonso, Sylvie
AU  - Alonso S
AD  - Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for 
      Research and Technology, Singapore; Department of Microbiology, National 
      University of Singapore, 5 Science Drive 2, Blk MD4, Level 3, Singapore 117545.
FAU - Chen, Jianzhu
AU  - Chen J
AD  - Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for 
      Research and Technology, Singapore; Department of Biology, Koch Institute of 
      Integrative Cancer Research, Massachusetts Institute of Technology, 77 
      Massachusetts Avenue, Cambridge MA 02139, USA.
FAU - Lescar, Julien
AU  - Lescar J
AD  - School of Biological Sciences, Nanyang Technological University, 60 Nanyang 
      Drive, Singapore 637551.
FAU - Shriver, Zachary
AU  - Shriver Z
AD  - Visterra Inc., One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
FAU - Ooi, Eng Eong
AU  - Ooi EE
AD  - Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for 
      Research and Technology, Singapore; Program in Emerging Infectious Diseases, 
      Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857.
FAU - Sasisekharan, Ram
AU  - Sasisekharan R
AD  - Department of Biological Engineering, Koch Institute of Integrative Cancer 
      Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 
      Cambridge MA 02139; USA; Infectious Diseases Interdisciplinary Research Group, 
      Singapore-MIT Alliance for Research and Technology, Singapore. Electronic 
      address: rams@mit.edu.
LA  - eng
SI  - PDB/4UDZ
GR  - R01 GM057073/GM/NIGMS NIH HHS/United States
GR  - R37 GM057073-13/GM/NIGMS NIH HHS/United States
GR  - 1R01AI111395/AI/NIAID NIH HHS/United States
GR  - T32 ES007020/ES/NIEHS NIH HHS/United States
GR  - R01 AI111395/AI/NIAID NIH HHS/United States
GR  - R37 GM057073/GM/NIGMS NIH HHS/United States
GR  - 2T32ES007020/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150716
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Receptors, Fc)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Neutralizing/*administration & dosage/*chemistry
MH  - Dengue/immunology/*therapy/virology
MH  - Dengue Virus/immunology/*physiology
MH  - Disease Models, Animal
MH  - Immunodominant Epitopes/*chemistry
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phagocytosis
MH  - Protein Engineering
MH  - Receptors, Fc/immunology
MH  - Sequence Alignment
PMC - PMC4758460
MID - NIHMS706754
EDAT- 2015/07/21 06:00
MHDA- 2015/10/29 06:00
PMCR- 2016/07/30
CRDT- 2015/07/21 06:00
PHST- 2014/11/21 00:00 [received]
PHST- 2015/05/13 00:00 [revised]
PHST- 2015/06/19 00:00 [accepted]
PHST- 2015/07/21 06:00 [entrez]
PHST- 2015/07/21 06:00 [pubmed]
PHST- 2015/10/29 06:00 [medline]
PHST- 2016/07/30 00:00 [pmc-release]
AID - S0092-8674(15)00827-2 [pii]
AID - 10.1016/j.cell.2015.06.057 [doi]
PST - ppublish
SO  - Cell. 2015 Jul 30;162(3):493-504. doi: 10.1016/j.cell.2015.06.057. Epub 2015 Jul 
      16.