Fig. 5: Cross-reactive PTRAMP, CSS, and Ripr antibodies exhibit differential inhibition in multiple species of Plasmodium.

a IgG antibodies in human patients with Plasmodium infections. Fold-change peak week one antibody response relative to the seropositivity cut-off (mean of negative controls + 2x standard deviation). b Mouse monoclonal antibodies mapped by binding region. Open text represents antibodies binding both P. vivax and P. knowlesi, and closed text represents cross-reactivity between all three species. Bold lines indicate 4E2 and 2D9 block PvPC binding to PvRipr and that 4H10 blocks PvRipr binding to PvPC. All other antibodies have no effect on PvPC-PvRipr binding and are assumed to be capable of binding the PvPCR complex. c P. knowlesi growth inhibition assay (GIA) of anti-PvPC and anti-PvRipr biologics. The non-inhibitory PfCSS nanobody H2 was included as a negative control¹⁸. Three independent experiments were performed with mean and SEM shown. Antibodies and nanobodies were tested at a final concentration of 0.5 mg/mL. Data are colored according to antigen (CSS in green, PTRAMP in pink and Ripr in yellow). d GIA dilution series for inhibitory antibodies in P. knowlesi. Growth inhibition (%) is the mean of six independent experiments for 5B3, 2D9, four independent experiments for 5B4 and two independent experiments for 4E2. Error bars represent standard deviation. e GIA dilution series for inhibitory antibodies in P. falciparum. Growth inhibition (%) is the mean of five independent experiments for 5B3, two independent experiments for 4E2, and one independent experiment for 4H10, 2D9 and non-immune IgG. Error bars represent standard deviation. f Ex vivo GIA of P. vivax parasites. Antibodies were tested at a final concentration of 0.5 mg/mL. Anti-Duffy antigen receptor for chemokines (DARC) mouse monoclonal antibody 2C3 was used as a positive control⁷². Data are from six independent experiments. Error bars show mean and SEM. Data are colored as in c. g P. cynomolgi GIA of anti-PvPC and anti-PvRipr antibodies. Antibodies were tested at a final concentration of 0.5 mg/mL. Three independent experiments were performed with mean and SEM shown. Data are colored as in c. Source data are provided as a Source Data file.