Protecting capacity against malaria of chemically defined tetramer forms based on the Plasmodium falciparum apical sushi protein as potential vaccine components

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies possible targets of allele-specific immunity to clinical malaria

“…Fifty-five of the genes containing significantly differentiated sites (38%) encode proteins of unknown function that are not associated with any computed or curated molecular function or biological process based on Gene Ontology ( S1 Table ). These 145 gene products included some proteins previously identified as potential vaccine candidates, including AMA1 (apical membrane antigen 1) [ 17 , 20 ], ASP (apical sushi protein, PF3D7_0405900) [ 41 ], CLAG8 (cytoadherence linked asexual protein 8, PF3D7_0831600) [ 42 , 43 ], SLARP (sporozoite and liver asparagine-rich protein, PF3D7_1147000) [ 44 ] and a conserved protein of unknown function (PF3D7_1359000) [ 45 ].…”

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies potential targets of allele-specific immunity to clinical malaria

“…Fifty-five of the genes containing significantly differentiated sites (38%) encode proteins of unknown function that are not associated with any computed or curated molecular function or biological process based on Gene Ontology (Supplementary Table 1). These 145 gene products included some proteins previously identified as potential vaccine candidates, including AMA1 (apical membrane antigen 1) (Takala et al, 2009; Thera et al, 2011, p. 20), ASP (apical sushi protein, PF3D7_0405900) (Vanegas et al, 2014), CLAG8 (cytoadherence linked asexual protein 8, PF3D7_0831600) (Gupta et al, 2015; Iriko et al, 2008), SLARP (sporozoite and liver asparagine-rich protein, PF3D7_1147000) (van Schaijk et al, 2014) and a conserved protein of unknown function (PF3D7_1359000) (Krzyczmonik et al, 2012).…”

The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes

“…Some studies have even highlighted that a single replacement of a peptide-bond modulates the three-dimensional structure of the peptide-antigen and has proven to be sufficient to achieve greater protective capacity compared to the native antigen [161]. Obtaining such envisioned modified molecules based on antigenic regions of malaria has allowed establishing structural conformations that are evidenced to be associated with immunogenic properties, as already reported [163], where tetramer structures based on the Plasmodium apical sushi protein were neither toxic nor hemolytic being also highly antigenic and malaria protective when administered in infected rodents, establishing deep differences regarding other previously studied vaccine candidates [164,165].…”

“…This experimental approach consisted of selecting potential antigen sequence targets from P. falciparum blood-stage proteins, which were then obtained by solid-phase synthesis and extensively characterized. Introduction of non-natural elements into given amino-acid pairs was then proposed and obtained by liquid and solid-phase synthesis strategies as previously reported [163]. To test the immunological potential of all selected and modified sequences, immunization of groups of four female BALB/c mice of 4 to 6 weeks of age per molecule were conducted using a classical scheme of 0, 15, 30, and 45 days with 50 micrograms of immunogen per animal co-formulated with the Freund's adjuvant (complete and incomplete versions).…”