Table 1.
Neutralizing EV71 capsid-specific human monoclonal antibodies
| mAb a | V H | D H | J H | Heavy-chain junction sequence | Mut b | λ/ƙ | V ƙ /V λ | J ƙ /J λ | Light-chain junction sequence | Mut b | Neut (µg ml −1 ) c |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Donor M | |||||||||||
| Group 1 | |||||||||||
| 16-2-11B | 1-46*01 or 03 | 2-21*02 | 4*02 | CARNYNGYCAGDCYSPDFW | 23 (16) | λ | 2-14*01 | 2*01 or 3*01 or 3*02 | CSAFTTSSTLVF | 18 (12) | 0.78/0.39 |
| 16-1-10B | 1-46*01 or 03 | 2-21*02 | 4*02 | CARNYNGYCAGECYSPDYW | 23 (10) | λ | 2-14*01 | 2*01 or 3*01 or 3*02 | CSSFTTSSTLVF | 20 (14) | 0.89/0.45 |
| Group 2 | |||||||||||
| 16-2-2D | 1-46*01 or 02 or 03 | 3-22*01 | 6*02 | CARGPGPGGKYYYDSSDAYYYYGMDVW | 28 (18) | λ | 1-44*01 | 1*01 | CAAWDDRLNAYVF | 13 (7) | 0.50/2.01 |
| Group 3 | |||||||||||
| 16-3-3C | 3-9*01 | 6-19*01 | 6*02 | CAKDGPSSGWSYQNYYNAMDVW | 22 (14) | λ | 2-11*01 | 2*01 or 3*01 or 3*02 | CCSYAGSDTLVF | 12 (8) | 2.01/1.00 |
| 16-3-5C | 3-9*01 | 6-19*01 | 6*02 | CAKDGPSSGWSYQNYYNAMDVW | 18 (11) | λ | 2-11*01 | 2*01 or 3*01 or 3*02 | CCSYAGSDTLVF | 9 (7) | 1.25/2.50 |
| Group 4 | |||||||||||
| 16-2-12D | 4-39*01 | 2-2*01 | 4*02 | CARHASPHCSSTSCYDGPYNKNWYVDLW | 21 (15) | λ | 1-47*02 | 2*01 or 3*01 | CAAWDDSLSGLVF | 13 (4) | 1.55/1.55 |
| Group 5 | |||||||||||
| 16-2-9D | 4-39*01 or 02 | 2-2*01 | 4*02 | CARHSSPQCSPTSCYEGPYTRDWYVDYW | 24 (16) | λ | 1-44*01 | 2*01 or 3*01 | CAAWDGSLNAVVF | 13 (8) | 0.90/0.90 |
| 16-2-6B | 4-39*01 or 02 | 2-2*01 | 4*02 | CARHSSPQCSPTSCYEGPYTRNWYVDYW | 23 (17) | λ | 1-44*01 | 2*01 or 3*01 | CAAWDDSLNAVVF | 8 (4) | 3.22/0.81 |
| Group 6 | |||||||||||
| 16-1-4A | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 19 (11) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 10 (8) | 8.25/− |
| 16-1-7A | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 22 (12) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 11 (8) | 6.60/− |
| 16-1-8A | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 23 (12) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 9 (7) | 10.00/− |
| 16-1-3B | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 25 (13) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 9 (7) | 7.15/− |
| 16-1-12B | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 24 (13) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 11 (8) | 9.25/− |
| 16-2-10A | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 25 (14) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 10 (7) | 9.55/− |
| 16-2-11D | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 23 (15) | λ | 1-44*01 | 3*02 | CAAWDDSLNTWVF | 10 (7) | 7.40/− |
| 16-3-10A | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 22 (13) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 12 (8) | 7.60/− |
| 16-3-4D | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 21 (12) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 10 (7) | 3.05/− |
| 16-3-8D | 4-39*01 | 6-19*01 | 6*02 | CARHVPVAGFGYYYYGMDVW | 27 (15) | λ | 1-44*01 | 3*02 | CAAWDDSLNNWVF | 10 (7) | 7.75/− |
| Group 7 | |||||||||||
| 16-2-8C | 4-39*03 | 2-2*01 | 4*02 | CVRHSSPQCSPTSCYEGPYTRDWYVDYW | 28 (16) | λ | 1-44*01 | 2*01 or 3*01 | CAAWDGSLNAVVF | 13 (8) | 0.09/0.09 |
| Group 8 | |||||||||||
| 16-3-10B | 7-4-1*02 | 1-14*01 | 5*02 | CAYDPLGNWFDPW | 21 (12) | λ | 2-23*01 or 03 | 1*01 | CCSYAGTRTYVF | 16 (9) | 0.03/0.03 |
| Donor Y | |||||||||||
| Group 1 | |||||||||||
| 17-1-12A | 3-11*05 | 1-26*01 | 6*02 | CAREKWEKLGKLYYYGLDVW | 30 (20) | ƙ | 2-28*01 or 2D-28*01 | 2*02 | CMQALQTPRTF | 6 (4) | 0.93/7.45 |
| 17-3-5A | 3-11*05 | 1-26*01 | 6*02 | CAREKWEKLGKLYYYGLDVW | 25 (18) | ƙ | 2-28*01 or 2D-28*01 | 2*02 | CMQALQTPRTF | 7 (4) | 0.95/7.60 |
| Group 2 | |||||||||||
| 17-2-12A | 3-23*04 | 3-16*01 | 6*02 | CAKSVAARRFYFYYGMDAW | 28 (18) | λ | 7-43*01 | 3*02 | CLLYYGGSQLWVF | 14 (8) | 10.25/− |
| 17-3-2A | 3-23*04 | 3-16*01 | 6*02 | CAKSVAARRFYFYYGMDAW | 22 (17) | λ | 7-43*01 | 3*02 | CLLYYGGSQLWVF | 13 (8) | 11.10/− |
| 17-3-10A | 3-23*04 | 3-16*01 | 6*02 | CAKSVAARRFYFYYGMDAW | 27 (16) | λ | 7-43*01 | 3*02 | CLLYYGGSQLWVF | 12 (6) | 13.40/− |
| 17-3-11D | 3-23*04 | 3-16*01 | 6*02 | CAKSVAARRFYFYYGMDAW | 24 (16) | λ | 7-43*01 | 3*02 | CLLYYGGSQLWVF | 9 (7) | 11.15/− |
| Group 3 | |||||||||||
| 17-2-2B | 4-39*01 | 3-10*01 | 4*02 | CARTYGSGSYWGYFEYW | 3 (3) | λ | 2-8*01 | 3*02 | CSSYAGSNNWVF | 1 (0) | 0.87/0.87 |
| Donor Z | |||||||||||
| Group 1 | |||||||||||
| 34-1-6D | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 4 (3) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 0 (0) | 4.70/9.40 |
| 34-2-3A | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGLDVW | 3 (2) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 1 (0) | 9.75/9.75 |
| 34-2-5A | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 5 (3) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSSPLTF | 3 (1) | 4.95/9.90 |
| 34-2-9B | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 2 (1) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSSPLTF | 2 (1) | 4.78/9.55 |
| 34-2-1C | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGLDVW | 2 (2) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 2 (0) | 7.10/7.10 |
| 34-2-5D | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 6 (3) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 1 (0) | 6.45/6.45 |
| 34-3-4A | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 1 (1) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSSPLTF | 3 (1) | 9.95/9.95 |
| 34-3-4B | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGLDVW | 7 (4) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 0 (0) | 9.70/9.70 |
| 34-3-6B | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGLDVW | 5 (4) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 0 (0) | 9.65/9.65 |
| 34-3-1C | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 4 (3) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 1 (0) | 8.10/16.20 |
| 34-3-8D | 7-4-1*02 | 1-7*01 | 6*02 | CARAKALLYYGMDVW | 1 (1) | ƙ | 1-39*01 or 1D-39*01 | 4*01 | CQQSYSTPLTF | 2 (1) | 7.65/7.65 |
DH, diversity gene segment of the heavy-chain variable domain; JH, joining gene segment of the heavy-chain variable domain; Mut, mutation number; J λ joining gene segment of the lambda light-chain variable domain; Neut, neutralization; VH, variable gene segment of the heavy-chain variable domain; Vƙ, variable gene segment of the kappa light-chain variable domain; Vλ, variable gene segment of the lambda light-chain variable domain; Jƙ joining gene segment of the kappa light-chain variable domain
aRepresentative neutralizing monoclonal antibodies (mAb) from each of the 12 variable domain-related groups are shown in bold
bThe number of nucleotide mutations in the heavy- and light-chain variable domains and the number of amino acid replacements (shown in parentheses). The variable domain consists of the framework regions (FR1, FR2, FR3, and FR4) and complementarity determining regions (CDR1, CDR2, and CDR3). To determine the individual gene segments employed by VDJ and VJ rearrangements and the number of nucleotide mutations and amino acid replacements, the variable domain sequences were aligned with germline gene segments using the international ImMunoGeneTics (IMGT) alignment tool
cThe lowest concentration of the mAb-containing supernatant that showed 100% inhibition of EV71 12-96015 (B5)/11-96023 (C4)-induced CPE. -: no neutralization