Table 1.
Antigenic and amino acid sequence variation among different clades of H5N1 vaccine candidate viruses.
Figure 1.
Structural comparison between H5 hemagglutinins.
(A) Structural alignment of Anhui05 (green), Egypt10 (blue) and Hubei10 (purple) onto Viet04 (yellow) reveals how structurally related these clades are. (B) Alignment of the receptor-binding site (RBS) reveals conserved structural features and residues. (C) Compared to Viet04, a total of eleven residue differences in and around the RBS are present. Amino acid residues in each structure are numbered consecutively according to the ectodomain fragment of the mature HA1 protein. *Deletion of Leu129 in Egypt10 produces a shift in the numbering of residues 129–324 in Egypt10 relative to structurally equivalent residues in Anhui05 and Hubei10.
Figure 2.
Structural variation among the different H5N1 clades.
(A) Surface representation of the Hubei10 trimeric HA indicating the positions of surface exposed residue substitutions among Clade 1 (Viet04), clade 2.3.4 (Anhui05), clade 2.2.1 (Egypt10) and clade 2.3.2.1 (Hubei10). Positions containing single substitutions are colored cyan and positions containing multiple substitutions are colored magenta. (B) Amino acid consensus sequences of H5N1 HA clades at positions equivalent to the HA antigenic sites, Ca, Cb, Sa and Sb, of human H1N1 viruses [39], are shown. Clade 1 (Viet04), clade 2.3.4 (Anhui05), clade 2.2.1 (Egypt10) and clade 2.3.2.1 (Hubei10) are highlighted in red. Structural positions of these equivalent sites are highlighted on the Hubei10 trimeric structure (Ca; pale yellow, Cb; wheat, Sa; pale green, Sb; pale blue). Asparagine residues that are potentially N-glycosylated are colored orange.
Figure 3.
Receptor specificity of H5 recHAs.
Glycan microarray analysis of recombinant Viet04 HA (A), Anhui05 (B), Egypt10 (C) and Hubei10 (D). Colored bars highlight glycans that contain α2–3 Neu5Ac (blue) and α2–6 Neu5Ac (red), α2–6/α2–3 mixed Neu5Ac (purple), N-glycolyl Neu5Ac (green), α2–8 Neu5Ac (brown), β2–6 and 9-O-acetyl Neu5Ac (yellow), and non-Neu5Ac (grey). Error bars reflect the standard error in the signal for six independent replicates on the array. The structures of each of the numbered glycans are found in Table S5.