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. 2023 Sep 15;19(9):e1011182. doi: 10.1371/journal.ppat.1011182

Fig 1. The major stages of invasion of Plasmodium falciparum blood stage parasites and growth inhibitory activity (GIA) of anti-PfRH5 and -PfCyRPA IgGs and Fab fragments.

Fig 1

(A) Several videos of P. falciparum in the presence of 400 μg/mL EBL 040 control IgG were analyzed to derive the average times for each of the major steps of pre-invasion, internalization, merozoite to ring transition and echinocytosis (EC) of the infected erythrocyte. After egress, merozoites took 42.0 s to contact the erythrocyte they invaded (all times are means). Following an initial contact of 0.9 s, the merozoites deformed their erythrocytes for 52.6 s followed by the quiescent complex stage of 1.8 s, when it is believed the PCRCR complex and tight junction form (“Rh5-basigin stage”). Merozoite internalization or invasion takes 10.3 s after which the merozoite starts to spin 16.4 s later. Spinning lasts 116.3 s and once finished, a pseudopod emerges from the merozoite 159.2 s later. 57.2 s after this, the merozoite membrane starts to become irregular to form a pre-ring. After 638.0 s, a fully formed complete ring is evident. 40.9 s after invasion is complete, the host erythrocyte develops membranous protrusions in a process called echinocytosis. These protrusions increase in their extent reaching a maximum after 44.2 s. This state continues for 395.9 s until the erythrocyte returns to its usual biconcave shape over 305.9 s. Of note, the timing and duration of echinocytosis is highly variable. SD, range and number (N) of events are indicated in S1 Table. (B) In vitro single cycle growth inhibition activity (GIA) assay dilution series of R5.008 mAb alone (pink), or in combination with Cy.009 mAb held at 0.13 mg/mL (blue), against 3D7 parasites. Predicted Bliss additivity is indicated (grey). The solid green line indicates the GIA of mAb Cy.009 held alone at a fixed concentration of 0.13 mg/mL. Dotted line indicates 50% GIA. (C) Comparison of the GIA of the Cy.007 mAb (purple) with its Fab fragment (light pink) indicating the latter is much more potent. Assay performed as in B.