TABLE 4.
Summary of H5N1 neutralizing antibodies targeting the HA head region
| MAb parameter | Value |
||||||
|---|---|---|---|---|---|---|---|
| 13D4 | AVFluIgG03 | H5.3 | 65C6 | 100F4 | FLD194 | H5M9 | |
| Neutralization breadth | 1997–2014 H5N1 | 1997–2008H5N1 | Only VN04/05 and its two variants | 1997–2007 H5N1 | 1997–2007 H5N1 | 1997–2007 H5N1 | 1997–2010 H5N1 |
| H5, all clades except 3, 4, 6 | H5, all clades except 1, 4, 8 | H5, all clades except 7.1 | H5, all clades except 7.1 | Clades 0, 1, 2. 3 .4 | H5, all clades except 0, 1, 2 | ||
| Source | Mouse | Human | Human | Human | Human | Human | Mouse |
| PDB accession no. for immune complex structure | 6A0Z | 5DUP | 4XNM | 5DUM | 5DUR | 5A3I | 4MHH |
| HA for cocrystallization | VN1194 HA | Anhui05 HA | VN1203 | Anhui05 HA | Anhui05 HA | VN1203 | VN1203 HA |
| Resolution (Å) | 2.33 | 3.05 | 2.51 | 3.00 | 2.80 | 2.89 | 3.60 |
| Antibody footprint on HA | E131, L133a, S136, S137, W153A, I155A, K156, N158, S159, N186, D187, E190, K193, L194, K222, Q226 | E131, S133, S133a, V135, S136, S137, T144, P145, W153, I155, K156, K157, N158, N159, K193, L194, K222, Q226 | Y98, L133a, V135, S136, S137, Q142, G143, K144, S145, W153, I155, K156, N158, S159, E190, K193, L194, G225, Q226 | I121, Q122, I123, P125, S125b, D129, P162, T163, K165, R166, S167, Y168, N169, T171, N172, N244, E246 | D77, E78, I80, N81, H117, E119, K120, I121, Q122, K125a, Y141, Q142, R149, T171, N172, Q173, E174, Y256, K259, V260a, K261 | I80, N81, K120, I121, Q122, I123, I124, S125b, S126, S128, Y141, Q142, K144, N150, R166, S167, Y168, N169, T171, E255, Y256, K259 | D53, D55, G55a, V56, K57, R62, E78, N81, P83, E83a, H117, E119, E273, Y274, N276, N278 |
| Conservation of critical residues for antibody binding (%) | W153 (100), K156 (99.3), K/R193 (50/38.4), L194 (95.5) | E131 (71.0), S133 (97.4), K156 (99.3, N159 (64.0) | K/R144 (12.3/48.5), K193 (50) | – | D77 (99.4), E119 (98.9) | Q122 (84.7) | D53 (62.4), E83a (99.6), Y274 (99.7), N276 (91.5) |
| Method for key amino acid identification | SPR and ELISA on alanine scanning mutants | Pseudovirus-based neutralization assay | Sequence alignment of multiple reactive strains | Pseudovirus-based neutralization assay | Pseudovirus-based neutralization assay | Neutralization activity using isolated virus | Yeast cell display |
| HCDR3 sequence | ARLGTTAVERDWYFDV | VRDDSYDGGGHYGLHNWFDS | ARVALFDILTGGWFDP | AYHRRGHFYGSGSAWDWFES | ARALLTTVTTFEY | ARHASCSARSCYWGPVDY | VRNYGSSYGYFDV |
| HCDR3 length (aa) | 16 | 20 | 16 | 20 | 13 | 18 | 13 |
| VH germ line | 1-9 | 3-23 | 4-4 | 5-10 | 4-61 | 5-51 | 1-22 |