Table 1.
Classification of PfCSP hmAbs used in this study
| ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| hmAb | Preferred tetrapeptide | Ig gene family | Apparent avidity (nM) | Two-step binder | Stoichiometry (no. of binding sites) | rPfCSPFL affinity (nM) | rPfCSP5/3 affinity (nM) | In vivo SPZ neutralization (bite challenge, Wang et al.8) | References | |||
|
| ||||||||||||
| VH | VL | Pep21 | Pep22 | Pep29 | Wang et al.8; Kisalu et al.9 | |||||||
| CIS43 | NPDP | 1–3 | κ4–1 | <0.001 | 1.5 | – | yes | 7.2 | 15 | 4 | high | Wang et al.8; Kisalu et al.9 |
| CIS42 | NPDP | 7–4–1 | λ2–23 | 0.26 | 0.90 | 2.29 | no | 11.1 | 8 | 66 | ND | Kisalu et al.9; this study |
| L9 | NVDP | 3–33 | κ1–5 | 6.0 | 0.28 | – | yes | 11.2 | 22 | 3 | high | Wang et al.8 |
| F10 | NVDP | 3–33 | κ1–5 | 1.50 | 11.32 | – | no | 3.4 | 14 | 4 | ND | Wang et al.8; this study |
| L48 | NVDP | 3–23 | λ1–47 | 4.25 | 2.75 | – | yes | 11.7 | 2 | 66 | ND | Wang et al.8; this study |
| 317 | NANP | 3–30/33 | κ1–5 | 1.2 | 0.49 | <0.001 | yes | 12.2 | 2 | 2 | high | Wang et al.8; Oyen et al.10 |
| 311 | NANP | 3–30/33 | λ1–40 | 4.1 | 3.0 | <0.001 | yes | 15.6 | 4 | 2 | moderate | Wang et al.8; Oyen et al.10 |
| mAb10 | NANP | 3–33 | κ1–5 | 1.6 | 8.2 | <0.001 | no | 15.2 | 6 | 42 | moderate | Wang et al.8; Kisalu et al.9 |
| 1210 | NANP | 3–30/33 | κ1–5 | 2.2 | 100 | 0.043 | no | 12.9 | 29 | 600 | low | Wang et al.8; Imkeller et al.11 |
| MGG4 | NANP | 3–30/33 | κ4–1 | 4.28 | 2.72 | <0.001 | no | 12.8 | 12 | 31 | ND | Tan et al.12; this study |
| MGU12 | NANP | 3–30/33 | κ1–5 | 2.1 | 3.9 | <0.001 | no | 10.8 | 7 | 90 | low | Wang et al.8; Tan et al.12 |
| mAb4 | NANP | 3–33 | κ2D-29 | – | 7.24 | 0.39 | no | 6.1 | 87 | 260 | ND | Kisalu et al.9; this study |
| mAb26 | NANP | 3–48 | κ1–5 | – | – | 5.07 | no | 5.2 | 1,100 | 520 | ND | Kisalu et al.9; this study |
Top: graphic of PfCSP depicting the binding profiles of hmAbs used in this study. Schematics depict the N terminus, central repeat region (containing 1 NPDP, 4 NVDP, and 38 NANP tetrapep-tides), and the C terminus of PfCSP from 3D7 reference isolate. Bottom: hmAb name; preferred PfCSP tetrapeptide (NPDP, NVDP, NANP); VH and VL gene families; apparent avidity (nM) for 15mer peptide 21 (NPDPNANPNVDNAN), peptide 22 (NANPNVDPNANPNVD), and peptide 29 (NANPNANPNANPNAN) measured by biolayer interferometry (BLI); two-step binder determined by isothermal titration calorimetry (ITC); stoichiometry (no. of binding sites) of hmAb binding to recombinant full-length PfCSP (rPfCSPFL) by ITC; affinity for rPfCSPFL in the first binding event by ITC; affinity for a truncated rPfCSP containing 1 NPDP, 5 NANP, and 3 NVDP (rPfCSP5/3) in the first binding event by ITC. Qualitative score of in vivo sporozoite neutralization is based on mosquito bite challenge data 72 h after passive transfer of 600 μg hmAb in Wang et al.8; high neutralization: >70% sterile protection; moderate neutralization: 31%–69% sterile protection; low neutralization: <30% sterile protection. ND, not determined; “-”, undetectable. Data are representative of 2–3 independent experiments.