PMID- 24266517
OWN - NLM
STAT- MEDLINE
DCOM- 20140613
LR  - 20191210
IS  - 1472-765X (Electronic)
IS  - 0266-8254 (Linking)
VI  - 58
IP  - 3
DP  - 2014 Mar
TI  - Human monoclonal single-chain antibodies specific to dengue virus envelope 
      protein.
PG  - 270-7
LID - 10.1111/lam.12186 [doi]
AB  - Dengue virus (DENV) infection is an arthropod-borne disease with increasing 
      prevalence worldwide. Attempts have been made to develop therapeutic molecules 
      for treatment for DENV infection. However, most of potentially therapeutic DENV 
      monoclonal antibody was originated from mouse, which could cause undesirable 
      effects in human recipients. Thus, fully human antibody is preferable for 
      therapeutic development. Human single-chain variable fragments (HuScFv) with 
      inhibitory effect to DENV infection were generated in this study. HuScFv 
      molecules were screened and selected from the human antibody phage display 
      library by using purified recombinant DENV full-length envelope (FL-E) and its 
      domain III (EDIII) proteins as target antigens for biopanning. HuScFv molecules 
      were then tested for their bindings to DENV particles by indirect ELISA and 
      immunofluorescent microscopy. EDIII-specific HuScFv exhibited neutralizing effect 
      to DENV infection in Vero cells in a dose-dependent manner as determined by 
      plaque formation and cell ELISA. Epitope mapping and molecular docking results 
      concordantly revealed interaction of HuScFv to functional loop structure in EDIII 
      of the DENV E protein. The neutralizing HuScFv molecule warrants further 
      development as a therapeutic biomolecule for DENV infection. SIGNIFICANCE AND 
      IMPACT OF THE STUDY: No approved vaccine and specific drug for dengue virus 
      (DENV) infection are available; thus, their developments are urgently required. 
      The human single-chain variable antibody fragments (HuScFv) specific to DENV 
      envelope (E) protein are potential to be developed as therapeutic biomolecules. 
      HuScFv that bound specifically to recombinant full-length DENV E (FL-E) and its 
      domain III (EDIII) were generated and testified for its inhibitory effect in DENV 
      infection. EDIII-specific HuScFv inhibited DENV infection in a dose-dependent 
      manner and has potential to be further developed as a therapeutic biomolecule for 
      DENV infection.
CI  - (c) 2013 The Society for Applied Microbiology.
FAU - Saokaew, N
AU  - Saokaew N
AD  - Division of Molecular Medicine, Department of Research and Development, Faculty 
      of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Graduate 
      Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj 
      Hospital, Mahidol University, Bangkok, Thailand.
FAU - Poungpair, O
AU  - Poungpair O
FAU - Panya, A
AU  - Panya A
FAU - Tarasuk, M
AU  - Tarasuk M
FAU - Sawasdee, N
AU  - Sawasdee N
FAU - Limjindaporn, T
AU  - Limjindaporn T
FAU - Chaicumpa, W
AU  - Chaicumpa W
FAU - Yenchitsomanus, P
AU  - Yenchitsomanus P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131125
PL  - England
TA  - Lett Appl Microbiol
JT  - Letters in applied microbiology
JID - 8510094
RN  - 0 (Antibodies, Viral)
RN  - 0 (Single-Chain Antibodies)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Viral/administration & dosage/*immunology
MH  - Chlorocebus aethiops
MH  - Dengue/immunology/prevention & control/virology
MH  - Dengue Virus/genetics/*immunology
MH  - Epitope Mapping
MH  - Humans
MH  - Immunization, Passive
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein Structure, Tertiary
MH  - Sequence Alignment
MH  - Single-Chain Antibodies/administration & dosage/genetics/*immunology
MH  - Vero Cells
MH  - Viral Envelope Proteins/chemistry/genetics/*immunology
OTO - NOTNLM
OT  - dengue virus
OT  - envelope protein
OT  - human single-chain variable fragments
OT  - monoclonal antibody
OT  - phage display
OT  - virus entry
EDAT- 2013/11/26 06:00
MHDA- 2014/06/15 06:00
CRDT- 2013/11/26 06:00
PHST- 2013/02/13 00:00 [received]
PHST- 2013/10/20 00:00 [revised]
PHST- 2013/10/23 00:00 [accepted]
PHST- 2013/11/26 06:00 [entrez]
PHST- 2013/11/26 06:00 [pubmed]
PHST- 2014/06/15 06:00 [medline]
AID - 10.1111/lam.12186 [doi]
PST - ppublish
SO  - Lett Appl Microbiol. 2014 Mar;58(3):270-7. doi: 10.1111/lam.12186. Epub 2013 Nov 
      25.