Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/143143
Title: CHARACTERIZATION AND OPTIMIZATION OF INTERACTION OF MONOCLONAL ANTIBODIES WITH INFLUENZA A HEMAGGLUTININ
Authors: SUBHA SANKAR PAUL
Keywords: HEMAGGLUTININ, MONOCLONAL ANTIBODY, ScFv, CROSS-CLADE, CROSS-SUBTYPE, AFFINITY MATURATION
Issue Date: 17-Jan-2018
Citation: SUBHA SANKAR PAUL (2018-01-17). CHARACTERIZATION AND OPTIMIZATION OF INTERACTION OF MONOCLONAL ANTIBODIES WITH INFLUENZA A HEMAGGLUTININ. ScholarBank@NUS Repository.
Abstract: The recent outbreaks of highly pathogenic H5N1, H7N7 and H7N9 avian influenza virus have raised serious concerns. Monoclonal antibodies (MAb) have been increasingly used successfully in therapeutic purposes. Hemagglutinin (HA) being immunodominant, plays important roles in influenza infection and thus makes it an attractive target for MAb. This study characterizes two mouse MAbs, 9F4 and 4F3, which showed broad neutralization of H5 from multiple clades and were observed to bind to HA protein. MAb 9F4, a homosubtypic IgG2b MAb, binds to a novel epitope in the vestigial esterase (VE) sub-domain of HA comprising at least three non-continuous amino acid residues, arginine (R) at position 62, being the critical residue, while tryptophan (W) at position 69 and phenylalanine (F) at position 79 cooperates with R62 to stabilize the epitope. Broad cross subtype binding capability of MAb 4F3 is confirmed against H7N7 and H7N9 HA and HA1 subunit protein. MAb 4F3 was also observed to neutralize rgPR8 virus expressing HA of H7N7 and H7N9. Additionally, a single-chain variable fragment (ScFv) of 4F3 was constructed and when expressed on phages, it showed binding to HA. Taken together, our study uses different approaches to characterize and engineer monoclonal antibodies targeting the HA protein.
URI: http://scholarbank.nus.edu.sg/handle/10635/143143
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
PAULSSP.pdf3.46 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

83
checked on Sep 18, 2020

Download(s)

2
checked on Sep 18, 2020

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.