Abstract
The number of malaria vaccine candidates in preclinical and clinical development is limited. To identify novel blood-stage malaria vaccine candidates, we constructed a library of 1,827P. falciparum proteins prepared using the wheat germ cell-free system (WGCFS). Also, a high-throughput AlphaScreen procedure was developed to measure antibody reactivity to the recombinant products. Purified IgGs from residents in malaria endemic areas have shown functional activity against blood-stage parasites as judged by an in vitro parasite Growth Inhibition Assay (GIA). Therefore, we evaluated the GIA activity of 51 plasma samples prepared from Malian adults living in a malaria endemic area against the WGCFS library. Using the AlphaScreen-based immunoreactivity measurements, antibody reactivity against 3 proteins was positively associated with GIA activity. Since anti-LSA3-C responses showed the strongest correlation with GIA activity, this protein was investigated further. Anti-LSA3-C-specific antibody purified from Malian adult plasmas showed GIA activity, and expression of LSA3 in blood-stage parasites was confirmed by western blotting. Taken together, we identified LSA3 as a novel blood-stage vaccine candidate, and we propose that this system will be useful for future vaccine candidate discovery.
Highlights
The number of malaria vaccine candidates in preclinical and clinical development is limited
Classic studies showing that passive transfer of γ-globulin isolated from adults who lived in a malaria endemic area dramatically reduced parasitemias and alleviated the symptoms in malaria-infected children have pointed to the role of antibodies in protective immune responses[4]
To identify novel blood-stage malaria vaccine candidates, in this study 1,827P. falciparum proteins were expressed using wheat germ cell-free system (WGCFS), and 51 purified IgGs were prepared from Malian adults who lived in a malaria endemic area
Summary
The number of malaria vaccine candidates in preclinical and clinical development is limited. Purified IgGs from residents in malaria endemic areas have shown functional activity against blood-stage parasites as judged by an in vitro parasite Growth Inhibition Assay (GIA). We evaluated the GIA activity of 51 plasma samples prepared from Malian adults living in a malaria endemic area against the WGCFS library. Anti-LSA3-C-specific antibody purified from Malian adult plasmas showed GIA activity, and expression of LSA3 in blood-stage parasites was confirmed by western blotting. The wheat germ cell-free system (WGCFS) has been used to express several malaria antigens, and the recombinant proteins produced could elicit in-vitro growth inhibitory antibodies in animals as judged by in vitro functional assays with P. falciparum parasites, such as the growth inhibition assay (GIA)[8,12]. Falciparum proteins were expressed using WGCFS, and 51 purified IgGs were prepared from Malian adults who lived in a malaria endemic area. We identified LSA3 as a novel blood-stage vaccine candidate through this study
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