Extended Data Fig. 9: The anti-IFX 8E12–IgG2a monoclonal antibody with abrogated immune effector recruitment sites reveals highly potent protection due to several mechanisms of immunological protection, including a major role for complement.

a, Groups of five mice were injected three times intravenously with the indicated doses of purified anti-IFX 8E12–IgG2a monoclonal antibody and challenged with the luciferase-expressing transgenic T. vivax parasites. Control is an isotype-matched mouse IgG2a monoclonal antibody. A cross indicates where a single mouse had to be removed from the study on day 16 for health reasons thought to be unrelated to the infection. b, Groups of five mice were administered three times intravenously with either 50 μg (left) or 100 μg (right) of purified anti-IFX 8E12–IgG2a monoclonal antibody containing mutations in immune effector recruitment binding sites and challenged with luciferase-expressing transgenic T. vivax parasites. Mutations prevented binding to C1q (ΔC1q), FcRs (ΔFcR) or both (ΔC1qΔFcR) and were compared to non-mutated 8E12–IgG2a, 8E12–IgG1 and both isotype-matched IgG2a and IgG1 controls. In all panels, data points represent individual mice and grey shading indicates bioluminescence thresholds of uninfected mice; dashed lines indicate survival within each group. Reductions in parasitaemia followed by rebounds after day 8 post-infection are likely to be due to the development of protective host antibody responses directed to the dominant VSG within the parasite population and selection of an antigenically distinct variant. One of two independent experiments with very similar outcomes is shown.

Source data