Summary of anti-VEEV mAbs
| mAb . | Isotype . | Group . | Critical binding residue(s)a . | E2 domain . | Mapping strategy . | Neutralizing EC50 (ng/ml) . | Stage inhibited . | Survival (%) . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SINV-VEEV TRD (IAB) . | VEEV TC-83 (IAB) . | SINV-VEEV INH9813 (IC) . | SINV-VEEV ZPC738 (ID) . | Prophylaxis (−24 h) . | Therapy (+24 h) . | |||||||
| mVEEV-8 | IgG2b | I | L5 | N | Escape | 976.7 | 2.9 | >10,000 | >10,000 | AV,N, L, F, E | 90 | 80 |
| mVEEV-10 | IgG2c | I | N60, K62 | A | Alanine | 796.2 | 229.0 | 4,662 | >10,000 | AV,N, F, E | NT | NT |
| mVEEV-19 | IgG2c | I | D56, N332 | A/C | Alanine | 206.4 | 8.6 | 87.0 | 880.9 | AV,N, L, F, E | NT | NT |
| mVEEV-36 | IgG2c | I | D56, K62 | A | Alanine | 71.7 | 8.9 | 40.1 | 670.9 | AV,N, L, F, E | 70 | 70 |
| mVEEV-68 | IgG2c | I | D56, K62, G63, R64, D94, N332 | A/C | Alanine | 142.2 | 56.8 | 355.5 | 3,192 | AV, L, F, E | 100 | 50 |
| mVEEV-43 | IgG1 | N/A | L5, F6, T49, I110, L287, P292, I311, N332 | N/A/C | Alanine | 1,836 | 308.8 | >10,000 | 1,539 | AV,N, E | 70 | 50 |
| mVEEV-1 | IgG2c | II | S182 | B | Alanine | 1.5 | 2.6 | 2.1 | 448.7 | AV,N, L, F | 100 | 40 |
| mVEEV-59 | IgG2b | II | K213, F217 | B | Alanine | 10.1 | 5.7 | 202.0 | >10,000 | AV,N, L, F | NT | NT |
| hVEEV-63 | IgG1 | II | K213 | B | Alanine | 1.1 | 0.7 | 0.9 | >10,000 | AV,N, F | 80 | 80 |
| mVEEV-TRD15 | IgG2c | II | T214 | B | Alanine | 2.0 | 385.8 | >10,000 | >10,000 | AV,N, L, F, E | NT | NT |
| mVEEV-57 | IgG2c | III | S184 | B | Escape | 3.9 | 16.8 | 10.2 | 12.4 | AV, L, F, E | 80 | 80 |
| mVEEV-71 | IgG2b | III | S184 | B | Escape | 3.5 | 10.3 | 6.7 | 28.0 | AV,N, L, F, E | 90 | 80 |
| mVEEV-TRD13 | IgG2b | III | K222 | B | Alanine | 560.8 | 1,601 | 1,249 | 956.1 | AV,N, E | NT | NT |
| mVEEV-TRD14 | IgG2c | III | G203, T205 | B | Escape | 23.5 | 161.8 | 1,058 | 247.4 | AN, F, E | NT | NT |
| mVEEV-TRD21 | IgG2c | III | T221, K222, Q225 | B | Escape | 44.6 | 220.5 | 22.9 | 95.3 | L, E | NT | NT |
| mAb . | Isotype . | Group . | Critical binding residue(s)a . | E2 domain . | Mapping strategy . | Neutralizing EC50 (ng/ml) . | Stage inhibited . | Survival (%) . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SINV-VEEV TRD (IAB) . | VEEV TC-83 (IAB) . | SINV-VEEV INH9813 (IC) . | SINV-VEEV ZPC738 (ID) . | Prophylaxis (−24 h) . | Therapy (+24 h) . | |||||||
| mVEEV-8 | IgG2b | I | L5 | N | Escape | 976.7 | 2.9 | >10,000 | >10,000 | AV,N, L, F, E | 90 | 80 |
| mVEEV-10 | IgG2c | I | N60, K62 | A | Alanine | 796.2 | 229.0 | 4,662 | >10,000 | AV,N, F, E | NT | NT |
| mVEEV-19 | IgG2c | I | D56, N332 | A/C | Alanine | 206.4 | 8.6 | 87.0 | 880.9 | AV,N, L, F, E | NT | NT |
| mVEEV-36 | IgG2c | I | D56, K62 | A | Alanine | 71.7 | 8.9 | 40.1 | 670.9 | AV,N, L, F, E | 70 | 70 |
| mVEEV-68 | IgG2c | I | D56, K62, G63, R64, D94, N332 | A/C | Alanine | 142.2 | 56.8 | 355.5 | 3,192 | AV, L, F, E | 100 | 50 |
| mVEEV-43 | IgG1 | N/A | L5, F6, T49, I110, L287, P292, I311, N332 | N/A/C | Alanine | 1,836 | 308.8 | >10,000 | 1,539 | AV,N, E | 70 | 50 |
| mVEEV-1 | IgG2c | II | S182 | B | Alanine | 1.5 | 2.6 | 2.1 | 448.7 | AV,N, L, F | 100 | 40 |
| mVEEV-59 | IgG2b | II | K213, F217 | B | Alanine | 10.1 | 5.7 | 202.0 | >10,000 | AV,N, L, F | NT | NT |
| hVEEV-63 | IgG1 | II | K213 | B | Alanine | 1.1 | 0.7 | 0.9 | >10,000 | AV,N, F | 80 | 80 |
| mVEEV-TRD15 | IgG2c | II | T214 | B | Alanine | 2.0 | 385.8 | >10,000 | >10,000 | AV,N, L, F, E | NT | NT |
| mVEEV-57 | IgG2c | III | S184 | B | Escape | 3.9 | 16.8 | 10.2 | 12.4 | AV, L, F, E | 80 | 80 |
| mVEEV-71 | IgG2b | III | S184 | B | Escape | 3.5 | 10.3 | 6.7 | 28.0 | AV,N, L, F, E | 90 | 80 |
| mVEEV-TRD13 | IgG2b | III | K222 | B | Alanine | 560.8 | 1,601 | 1,249 | 956.1 | AV,N, E | NT | NT |
| mVEEV-TRD14 | IgG2c | III | G203, T205 | B | Escape | 23.5 | 161.8 | 1,058 | 247.4 | AN, F, E | NT | NT |
| mVEEV-TRD21 | IgG2c | III | T221, K222, Q225 | B | Escape | 44.6 | 220.5 | 22.9 | 95.3 | L, E | NT | NT |
A, E2 domain A; alanine, alanine scanning mutagenesis; AN, attachment on N2A ΔB4galt7 cells; AV, attachment on Vero cells; B, E2 domain B; C, E2 domain C; E, egress; escape, escape mutagenesis; F, fusion; L, LDLRAD3-D1-Fc binding; N, E2 N-linker; NT, not tested.
Residues were defined as critical for mAb binding if a mutation caused >75% loss of binding via alanine scanning mutagenesis (or >85% for mVEEV-43 and mVEEV-68) and/or a mutation was present in >60% of an escape viral population (or >20% for mVEEV-TRD21).