Abstract
In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1). In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.
Highlights
In the past few years Trophozoite exported protein 1 (Tex1) encoded by PFF0165c was characterized as a novel malaria vaccine candidate
One of the synthetic peptides, P27, is spanning the coiled coil domain (K845 to T871), the other, P27A, corresponds to N-terminal intrinsically unstructured region (H223 to S326). Both peptides were tested in an extensive preclinical evaluation protocol to analyze the properties of anti-P27 and antiP27A antibodies regarding in vitro parasite killing in presence of monocytes [1,3], correlation with protection in adults and children [3,4], prevalence of peptide recognition by sera from semiimmune adults from different endemic region throughout the world [1,3] and sequence conservation in different culture strains and field isolates [3,5]
We show that Tex1 associates to Maurer’s clefts (MC) membrane facing the cytosol of the RBC
Summary
In the past few years Tex encoded by PFF0165c was characterized as a novel malaria vaccine candidate. Both peptides were tested in an extensive preclinical evaluation protocol to analyze the properties of anti-P27 and antiP27A antibodies regarding in vitro parasite killing in presence of monocytes [1,3], correlation with protection in adults and children [3,4], prevalence of peptide recognition by sera from semiimmune adults from different endemic region throughout the world [1,3] and sequence conservation in different culture strains and field isolates [3,5] Both fragments of Tex, peptides P27A and P27, are considered promising novel malaria blood stage vaccine candidates. A phase 1 clinical study of P27A is scheduled in 2011
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