PMID- 28525756
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20240314
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 169
IP  - 5
DP  - 2017 May 18
TI  - Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop 
      as a Site of Vulnerability.
PG  - 891-904.e15
LID - S0092-8674(17)30524-X [pii]
LID - 10.1016/j.cell.2017.04.038 [doi]
AB  - While neutralizing antibodies are highly effective against ebolavirus infections, 
      current experimental ebolavirus vaccines primarily elicit species-specific 
      antibody responses. Here, we describe an immunization-elicited macaque antibody 
      (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus 
      glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston 
      viruses. CA45, alone or in combination with an antibody that blocks receptor 
      binding, provided full protection against all pathogenic ebolaviruses in mice, 
      guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque 
      suggests that elicitation of broadly neutralizing antibodies (bNAbs) for 
      ebolaviruses is possible but difficult, potentially due to the rarity of bNAb 
      clones and their precursors. Unexpectedly, germline-reverted CA45, while 
      exhibiting negligible binding to full-length GP, bound a proteolytically 
      remodeled GP with picomolar affinity, suggesting that engineered ebolavirus 
      vaccines could trigger rare bNAb precursors more robustly. These findings have 
      important implications for developing pan-ebolavirus vaccine and 
      immunotherapeutic cocktails.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Zhao, Xuelian
AU  - Zhao X
AD  - Institute for Bioscience and Biotechnology Research, University of Maryland, 
      Rockville, MD 20878, USA.
FAU - Howell, Katie A
AU  - Howell KA
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA.
FAU - He, Shihua
AU  - He S
AD  - Special Pathogens Program, National Microbiology Laboratory, Public Health Agency 
      of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, 
      University of Manitoba, MB R3E 0J9, Canada.
FAU - Brannan, Jennifer M
AU  - Brannan JM
AD  - US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, 
      USA.
FAU - Wec, Anna Z
AU  - Wec AZ
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461, USA.
FAU - Davidson, Edgar
AU  - Davidson E
AD  - Integral Molecular, Philadelphia, PA 19104, USA.
FAU - Turner, Hannah L
AU  - Turner HL
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA.
FAU - Chiang, Chi-I
AU  - Chiang CI
AD  - Institute for Bioscience and Biotechnology Research, University of Maryland, 
      Rockville, MD 20878, USA.
FAU - Lei, Lin
AU  - Lei L
AD  - Institute for Bioscience and Biotechnology Research, University of Maryland, 
      Rockville, MD 20878, USA.
FAU - Fels, J Maximilian
AU  - Fels JM
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461, USA.
FAU - Vu, Hong
AU  - Vu H
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA.
FAU - Shulenin, Sergey
AU  - Shulenin S
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA.
FAU - Turonis, Ashley N
AU  - Turonis AN
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA.
FAU - Kuehne, Ana I
AU  - Kuehne AI
AD  - US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, 
      USA.
FAU - Liu, Guodong
AU  - Liu G
AD  - Special Pathogens Program, National Microbiology Laboratory, Public Health Agency 
      of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, 
      University of Manitoba, MB R3E 0J9, Canada.
FAU - Ta, Mi
AU  - Ta M
AD  - Integral Molecular, Philadelphia, PA 19104, USA.
FAU - Wang, Yimeng
AU  - Wang Y
AD  - Institute for Bioscience and Biotechnology Research, University of Maryland, 
      Rockville, MD 20878, USA.
FAU - Sundling, Christopher
AU  - Sundling C
AD  - Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New 
      South Wales 2010, Australia.
FAU - Xiao, Yongli
AU  - Xiao Y
AD  - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious 
      Diseases, NIH, Bethesda, MD 20892, USA.
FAU - Spence, Jennifer S
AU  - Spence JS
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461, USA.
FAU - Doranz, Benjamin J
AU  - Doranz BJ
AD  - Integral Molecular, Philadelphia, PA 19104, USA.
FAU - Holtsberg, Frederick W
AU  - Holtsberg FW
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA.
FAU - Ward, Andrew B
AU  - Ward AB
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA.
FAU - Chandran, Kartik
AU  - Chandran K
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461, USA.
FAU - Dye, John M
AU  - Dye JM
AD  - US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, 
      USA.
FAU - Qiu, Xiangguo
AU  - Qiu X
AD  - Special Pathogens Program, National Microbiology Laboratory, Public Health Agency 
      of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, 
      University of Manitoba, MB R3E 0J9, Canada.
FAU - Li, Yuxing
AU  - Li Y
AD  - Institute for Bioscience and Biotechnology Research, University of Maryland, 
      Rockville, MD 20878, USA; Department of Microbiology and Immunology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: 
      liy@ibbr.umd.edu.
FAU - Aman, M Javad
AU  - Aman MJ
AD  - Integrated BioTherapeutics, Rockville, MD 20850, USA. Electronic address: 
      javad@integratedbiotherapeutics.com.
LA  - eng
GR  - HHSN272201400058C/AI/NIAID NIH HHS/United States
GR  - R01 AI126587/AI/NIAID NIH HHS/United States
GR  - R43 AI124765/AI/NIAID NIH HHS/United States
GR  - U19 AI109762/AI/NIAID NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Ebola Vaccines)
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (Immunoglobulin Fab Fragments)
SB  - IM
CIN - Cell. 2017 May 18;169(5):773-775. PMID: 28525748
CIN - Trends Mol Med. 2017 Aug;23 (8):669-671. PMID: 28697885
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Neutralizing/chemistry/*immunology/*isolation & purification
MH  - Antibodies, Viral/chemistry/*immunology/*isolation & purification
MH  - Complementarity Determining Regions
MH  - Cross Reactions
MH  - Ebola Vaccines/*immunology
MH  - Ebolavirus/immunology
MH  - Epitope Mapping
MH  - Epitopes, B-Lymphocyte/immunology
MH  - Female
MH  - Ferrets
MH  - Guinea Pigs
MH  - Hemorrhagic Fever, Ebola/*immunology
MH  - Immunoglobulin Fab Fragments/ultrastructure
MH  - Macaca fascicularis
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Molecular
PMC - PMC5803079
MID - NIHMS939046
EDAT- 2017/05/20 06:00
MHDA- 2017/07/14 06:00
PMCR- 2018/02/07
CRDT- 2017/05/20 06:00
PHST- 2016/12/20 00:00 [received]
PHST- 2017/03/20 00:00 [revised]
PHST- 2017/04/27 00:00 [accepted]
PHST- 2017/05/20 06:00 [entrez]
PHST- 2017/05/20 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2018/02/07 00:00 [pmc-release]
AID - S0092-8674(17)30524-X [pii]
AID - 10.1016/j.cell.2017.04.038 [doi]
PST - ppublish
SO  - Cell. 2017 May 18;169(5):891-904.e15. doi: 10.1016/j.cell.2017.04.038.