Targeted T and B cell epitopes on CS protein.

(A) Schematic representation of the existing (upper panel) and novel (lower panel) hybrid Pb/Pf sporozoites. Native P. berghei sequence is indicated by light shading and transgenic P. falciparum sequence by dark shading. Neutralizing or presumptive neutralizing B-cell epitopes are denoted by black bars and human and murine CD4⁺ T cell epitopes by white bars. The “repeats” epitope (140–159) is part of a much larger motif, delineated by the dotted line. Numbering is based on the amino acid sequence of CSP from the 7G8 clone. (B) VLPs described in the manuscript. S2 Fig presents the amino acid sequences of the epitopes. In summary, Mal: NANP and NVDP repeats; Mal5: NANP repeat only; Ct: carboxy-terminal; TH: TH.3R and UTC epitopes; 3T: insertion of all 3 T cell eptiopes; C61S: Cys-to-Ser mutation at position 61 of WHcAg; Pv: P. vivax B cell repeats. Each of the epitopes is genetically inserted into the sequence of the VLP gene and a fully-assembled VLP consists of 120 homodimers, meaning each VLP presents 240 copies of the inserted epitope(s).