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. 2024 Jan 2;30(1):117–129. doi: 10.1038/s41591-023-02659-z

Fig. 2. Functional mAbs bind CSP-derived peptides not present in RTS,S.

Fig. 2

a, Percentage inhibition in the sporozoite liver burden mouse model and number of nucleotide mutations from germline are shown for mAbs reactive to either NANP6 repeat-region peptide (circles, n = 67) and C-terminal-region peptide (squares, n = 10), and are indicated as originating from vaccinees who were either protected (green, n = 54) or unprotected (blue, n = 23) and who received either the standard (012M, closed symbols, n = 30) or fractional (Fx017M, open symbols, n = 47) dose. b, SPR-determined binding potencies (Kd) of mAbs (n = 141) selected from 35 of the most efficacious lineages tested against CSP and a panel of CSP-derived peptides that are either homologous (NANP6, NPNA3) or heterologous (NVDP3NANP2, NPDPNANPNVDPNANP, junction [KQPADGNPDPNANPN]) to RTS,S. Examples are shown of a mAb with a broadly promiscuous binding profile (green, AB-007163), another with a profile relatively biased toward homologous peptides (purple, AB-007143) and a third with a profile between these extremes (blue, AB-007175). cg, Simple two-tailed linear regression comparing the number of nucleotide mutations from germline (SHM) per heavy chain versus log-transformed SPR binding off-rate (koff) against peptides. c, Short, major repeat (NPNA3, n = 140). d, Junctional (KQPADGNPDPNANPN, n = 68). e, Short, minor repeat (NPDPNANPNVDPNANP, n = 109). f, Long, major repeat (NANP6, n = 141). g, Long, minor repeat (NVDP3NANP2, n = 129). See Extended Data Table 1 for correlation analyses with nontransformed data. Dissociation rate (koff) measurements were limited to a minimum of 10−5 s−1. MAbs, with rates ≤10−5 s−1 included in the graphic but excluded from correlation analyses.