Screening and modification of antibody to target the conserved regions of hemagglutin

Abstract

High mutation level enables influenza A virus to dodge antibiotics that used to be effective against influenza A virus. A portion of hemagglutinin is believed to be structurally well-conserved in order to maintain its role in cellular fusion. This thesis screened anti-HA antibody and modified them to target the conserved regions of hemagglutinin of H1, H2 and H3 strains in order to overcome mutation and to treat multiple strains of influenza A virus. The conserved residues were identified by Matt alignment program. Disembodied amino acids and complementary determining regions (CDR) of antibody were docked against conserved regions to identify hotspot residues and scaffolds, respectively. The hotspots were grafted into the sequence of scaffolds which were then modelled by MODELLER to produce modelled CDR structures which in turn were docked against hemagglutinin structure of different strains. Three hotspot residues were identified and one was successfully grafted into one CDR. The grafted CDR showed ability to form contact with a conserved residue of H1 and H2 HA. This thesis is among the first researches to prove that it is possible to design antibody CDR as scaffolds to bind to HA structure. Keywords: Influenza A virus1 Hemagglutinin2 Antibody Conserved residues Docking