Fig. 4: distribution of epitopes for transmission-blocking antibodies across Pfs48/45.

A The structure of Pfs48/45 bound to 10D8 is used as a template, and combined with structures of the D3 domain of Pfs48/45 bound to either 85RF45.1 or 32F3 to generate a model, showing the relative locations of the three antibody epitopes. B A measure of the flexibility of the residues which form the epitopes for 32F3, 85RF45.1 and 10D8, as derived from molecular dynamics simulations. Each epitope was analysed in all 15 replicates and significance levels are based on a two-sided Mann–Whitney U tests where *** indicates p < 0.0005 and **** indicates p < 0.00005. The box bounds are interquartile ranges, and the lines within boxes are the median values. Whiskers extend to 1.5-fold the interquartile range. For 32F3 vs 85RF45.1 p = 0.00008; for 32F3 vs 10D8 p = 0.00031; for 10D8 vs 85RF45.1 p = 0.58974. C A composite model, derived from negative-stain electron microscopy structures. In each case, the complexes contained Pfs48/45 bound to 85RF45.1, together with either 9A6, 3H6, 10D8, 1F10 and 6A10. These were imaged by negative stain electron microscopy, and models were fitting into the resultant envelopes. These models were used to align the envelopes, allowing us to derive a composite model, showing the location for the five epitopes.