Development of novel malaria pre-erythrocytic vaccine antigens targeting Plasmodium sporozoite liver infection

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Previously, using a phage peptide display library, our group has identified Plasmodium parasite ligands and corresponding host cell receptors important for sporozoite-Kupffer cell interaction in the mammalian liver. Using a similar approach, we identified the HP1 peptide, a structural mimic of a ligand that the sporozoite uses to infect hepatocytes. Immunization with the HP1 peptide protects ~ 50 % mice from P. berghei challenge. Using an anti-HP1 antibody, we identified Plasmodium Phospholipid Scramblase (PLS) as the sporozoite ligand of hepatocytes and a potential vaccine antigen. We propose 1) to identify PLS protein epitopes that function in hepatocyte recognition, for use as a vaccine antigen; and 2) to develop a tri- functional vaccine antigen containing i) a sporozoite circumsporozoite protein (CSP) epitope, targeting liver sinusoid binding, ii) a sporozoite GAPDH-related epitope, targeting sporozoite exit from the circulation via Kupffer cell traversal, and iii) sporozoite PLS epitope, targeting hepatocyte infection. We expect that this approach will lead to enhancement of the moderate protective efficacy of the most advanced RTS,S/AS01 malaria vaccine.