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. 2022 Jun 23;219(8):e20220323. doi: 10.1084/jem.20220323

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© 2022 Banach et al.

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Figure 5. — Structural and functional analysis of the mechanisms of improved antimalaria protection. (a) X-ray structures of CIS43_Var2 and CIS43_Var10 in complex with the junctional epitope (Pep21) determined at 1.40 and 1.55 Å resolution. CIS43_Var11 and CIS43_Var18 structures were modeled using CIS43_Var2 as template. The location of the mutations is shown in red. The Pep21 numbering corresponds to PfCSP sequence. (b) Overlay of CIS43_Var2 with CIS43 showed interactions of Arg2 with Asp100_B, resulting in significant movement of CDR-H3 (left); CIS43_Var10 overlayed with CIS43 showed similar interactions between Arg2 and Asp100_B, without substantial changes to the CDR-H3 (right). (c) BLI affinity of improved CIS43 variant Fabs was measured against fl_PfCSP, NTDS_5/3_CSP, NPDP19, Pep21, Pep25, and Pep29 antigens. The affinity of multi-mutation variants was improved over CIS43 for all antigens except Pep 29.