Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25

• DOI: 10.1038/s41467-017-01924-3
• Publication Date: 2017-11-13T03:53:09Z
• Authors: Stephen W. Scally; Brandon McLeod; Alexandre Bosch; Kazutoyo Miura; Qi Liang; Sean Carroll; Sini Reponen; Ngan Nguyen; Eldar Giladi; Sebastian Rämisch; Vidadi Yusibov; Allan Bradley; Franck Lemiale; William R. Schief; Daniel Emerling; Paul Kellam; C. Richter King; Jean-Philippe Julien
• Keywords: Immunogen; Merozoite surface protein

The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. vaccination intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. three-dimensional structure has remained elusive, hampering molecular understanding of its function and limiting immunogen design. We report six crystal structures in complex with elicited immunization via virus-like particles human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated two distinct immunogenic sites on Pfs25. Importantly, one these broadly overlaps epitope well-known 4B7 mouse antibody, which can be targeted simultaneously target non-overlapping site additively increase inhibition. characterization inhibitory informs natural disposition surface ookinetes provides blueprints design next-generation immunogens.