Figure 1

Proof-of-concept CIS43 GL DMAb protects mice in mosquito bite challenge. (A) Schematic demonstrating CIS43 GL binding domain on CSP. (B) Binding ELISA of pooled supernatants harvested from Expi293F transfection to rCSP (mean ± SD). (C) In vivo expression of CIS43 GL in BALB/c mice at the peak expression timepoint Day 21 (left) through Day 120 (right). Mice were immunized with 100 µg CIS43 intramuscularly in the tibialis anterior with CD4+/CD8+ T cell depletion (n = 5 mice/group; geometric mean ± geometric SD). (D) In vivo expression of CIS43 GL in BALB/c mice without CD4+/CD8+ T cell depletion (n = 5 mice/group; geometric mean ± geometric SD). Mice were administered 100 µg or 200 µg intramuscularly in the tibialis anterior and/or quadricep. *p = 0.032 by two-tailed Mann–Whitney test. (E) Experimental layout of challenge. Mice were immunized with CIS43 GL and challenged 7 days post administration with mosquitos carrying PbPfLuc parasites. Positive control recombinant mAb 311 was administered 16 h prior to challenge. Blood smears for blood stage parasitemia were performed from days 4–10 post challenge. (F) Total flux quantified by IVIS; ** p = 0.0079 by two-tailed Mann–Whitney test (geometric mean ± geometric SD) (G) Percent inhibition of liver infection relative to infection of pVAX control infected mice (geometric mean ± geometric SD). (H) Percent of blood stage parasite free mice, determined through blood smears (n = 5 mice/group). **p < 0.01 versus pVAX by Log-rank (Mantel–Cox) test). The positive and negative controls were historical as we have published in Ref.⁴⁷.