Fig. 3. Transmission-reducing activity of monoclonal antibody 2A2 (Pfs230) is strain dependent.

a Transmission-reducing activity (TRA) of monoclonal antibody (mAb) 2A2 in standard membrane feeding assays with six laboratory-adapted parasite strains from different geographical regions that were fed to A. stephensi mosquitoes. Lines represent the fitted linear models and shaded areas the 95% credible intervals. IC₈₀ values are shown with 95% credible intervals between brackets. For strains NF175 and NF176, no meaningful IC₈₀ values of mAb 2A2 could be obtained due to very low efficacy. The raw data SMFA experiments can be found in the Supplementary Material (Supplementary Dataset 2). b Female gamete surface immunofluorescent assay using laboratory-adapted parasite strains incubated with 25 µg/mL of mAb 2A2 or serum from mice that were immunized with a fragment of Pfs230 (Pro+I, amino acids 443–736). Note that NF176 was incubated with 125 µg/mL mAb 2A2 (indicated with red asterisk). White arrows in bright field images indicate activated female gametes. Scale bars represent 10 µm. c Amino acid sequence alignment of Pfs230 domain IV (amino acids 1134–1268) of laboratory-adapted parasite strains. Non-synonymous single-nucleotide polymorphism (SNP)-encoded amino acids are specified and invariant amino acids are shown as dots. d Surface model of Pfs230 domain IV, based on the crystal structure of Pf41 (Pf3D7_0404900; PDB id: 4YS4), highlighting amino acids that vary among the tested strains. Histidine 1159 (H1159) is mutated to aspartate in all strains that are not sensitive to mAb 2A2 and is highlighted in red. Other amino acid variants are shown in blue. Histidine 1180 (H1180) is located in a non-structured loop, which is presented as a dashed line.