PMID- 24492300
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20211021
IS  - 1942-0870 (Electronic)
IS  - 1942-0862 (Print)
IS  - 1942-0862 (Linking)
VI  - 6
IP  - 2
DP  - 2014 Mar-Apr
TI  - Generation of human single-chain variable fragment antibodies specific to dengue 
      virus non-structural protein 1 that interfere with the virus infectious cycle.
PG  - 474-82
LID - 10.4161/mabs.27874 [doi]
AB  - Severe forms of dengue virus (DENV) infection frequently cause high case fatality 
      rate. Currently, there is no effective vaccine against the infection. Clinical 
      cases are given only palliative treatment as specific anti-DENV immunotherapy is 
      not available and it is urgently required. In this study, human single-chain 
      variable fragment (HuScFv) antibodies that bound specifically to the conserved 
      non-structural protein-1 (NS1) of DENV and interfered with the virus replication 
      cycle were produced by using phage display technology. Recombinant NS1 (rNS1) of 
      DENV serotype 2 (DENV2) was used as antigen in phage bio-panning to select phage 
      clones that displayed HuScFv from antibody phage display library. HuScFv from two 
      phagemid transformed E. coli clones, i.e., clones 11 and 13, bound to the rNS1 as 
      well as native NS1 in both secreted and intracellular forms. Culture fluids of 
      the HuScFv11/HuScFv13 exposed DENV2 infected cells had significant reduction of 
      the infectious viral particles, implying that the antibody fragments affected the 
      virus morphogenesis or release. HuScFv epitope mapping by phage mimotope 
      searching revealed that HuScFv11 bound to amino acids 1-14 of NS1, while the 
      HuScFv13 bound to conformational epitope at the C-terminal portion of the NS1. 
      Although the functions of the epitopes and the molecular mechanism of the 
      HuScFv11 and HuScFv13 require further investigations, these small antibodies have 
      high potential for development as anti-DENV biomolecules.
FAU - Poungpair, Ornnuthchar
AU  - Poungpair O
AD  - Division of Molecular Medicine; Department of Research and Development; Faculty 
      of Medicine Siriraj Hospital; Mahidol University; Bangkok, Thailand.
FAU - Bangphoomi, Kunan
AU  - Bangphoomi K
AD  - Department of Biochemistry; Faculty of Sciences; Kasetsart University; Bangkok, 
      Thailand.
FAU - Chaowalit, Prapaipit
AU  - Chaowalit P
AD  - Division of Molecular Medicine; Department of Research and Development; Faculty 
      of Medicine Siriraj Hospital; Mahidol University; Bangkok, Thailand.
FAU - Sawasdee, Nunghathai
AU  - Sawasdee N
AD  - Division of Molecular Medicine; Department of Research and Development; Faculty 
      of Medicine Siriraj Hospital; Mahidol University; Bangkok, Thailand.
FAU - Saokaew, Nichapatr
AU  - Saokaew N
AD  - Immunology Graduate Program; Department of Immunology; Faculty of Medicine 
      Siriraj Hospital; Mahidol University; Bangkok, Thailand.
FAU - Choowongkomon, Kiattawee
AU  - Choowongkomon K
AD  - Department of Biochemistry; Faculty of Sciences; Kasetsart University; Bangkok, 
      Thailand.
FAU - Chaicumpa, Wanpen
AU  - Chaicumpa W
AD  - Laboratory for Research and Technology Development; Department of Parasitology; 
      Faculty of Medicine Siriraj Hospital; Mahidol University; Bangkok, Thailand.
FAU - Yenchitsomanus, Pa-thai
AU  - Yenchitsomanus PT
AD  - Division of Molecular Medicine; Department of Research and Development; Faculty 
      of Medicine Siriraj Hospital; Mahidol University; Bangkok, Thailand.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140115
PL  - United States
TA  - MAbs
JT  - mAbs
JID - 101479829
RN  - 0 (Epitopes)
RN  - 0 (NS1 protein, Dengue virus type 2)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Single-Chain Antibodies)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Aedes
MH  - Animals
MH  - Cell Line
MH  - Cell Surface Display Techniques
MH  - Dengue/immunology/*metabolism/transmission
MH  - Dengue Virus/pathogenicity/*physiology
MH  - Epitope Mapping
MH  - Epitopes/immunology/*metabolism
MH  - Escherichia coli/*genetics
MH  - Humans
MH  - Hybridomas
MH  - Immunotherapy/*methods
MH  - Protein Conformation
MH  - Recombinant Proteins/immunology/*metabolism
MH  - Single-Chain Antibodies/*isolation & purification
MH  - Viral Nonstructural Proteins/immunology/*metabolism
MH  - Virion/drug effects
PMC - PMC3984335
OTO - NOTNLM
OT  - HuScFv
OT  - NS1
OT  - dengue virus
OT  - human single-chain variable fragment antibody
OT  - monoclonal antibody
OT  - non-structural protein-1
OT  - phage display
EDAT- 2014/02/05 06:00
MHDA- 2014/11/19 06:00
PMCR- 2015/03/01
CRDT- 2014/02/05 06:00
PHST- 2014/02/05 06:00 [entrez]
PHST- 2014/02/05 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - 27874 [pii]
AID - 2013MABS0489R [pii]
AID - 10.4161/mabs.27874 [doi]
PST - ppublish
SO  - MAbs. 2014 Mar-Apr;6(2):474-82. doi: 10.4161/mabs.27874. Epub 2014 Jan 15.