Figure 3: Definition of four major vulnerable sites (VS) on the globular head of H5 HA.

(a) Structural modeling of 65C6, AVFluIgG03, 100F4 and H5M9 binding to the A/Anhui/1/05 HA trimer. For clarity, binding to two different monomers is shown. HA1 is coloured in light yellow and HA2 in light cyan. The Fabs of 65C6, AVFluIgG03, 100F4 and H5M9 are shown in green, magentas, blue and red, respectively. (b) Spatial relationship of 65C6, AVFluIgG03, 100F4 and H5M9 epitopes on the A/Anhui/1/05 HA monomer. The colour for each epitope corresponds to the colour of respective mAb shown in a. The overlapping residues between 65C6 and 100F4 epitopes are shown in cyan, and that between 100F4 and H5M9 are shown in brown. (c) Sequence comparison of 65C6, AVFluIgG03, 100F4 and H5M9 epitopes with those published elsewhere. Residues within the 65C6, AVFluIgG03, 100F4 and H5M9 epitopes are coloured exactly the same as that for b. Residues recognized by other human or mouse mAbs published elsewhere are indicated by asterisks underneath the sequence. (d) Structural and spatial modeling of the four VS on the A/Anhui/1/05 HA trimer. Each VS was coloured exactly the same way as that of representing mAbs; VS1-65C6 (green), VS2-AVFluIgG03 (magentas), VS3-100F4 (blue) and VS4-H5M9 (red). (e) Structural and spatial modeling of the five antigenic domains on H3 Ha; Site A (green), Site B (magentas), Site C (red), Site D (orange) and Site E (blue). (f) Structural and spatial modeling of the five antigenic sites on H1 HA; Sa (green), Sb (magentas), Ca1 (orange), Ca2 (cyan) and Cb (blue).