Last Updated: 29/05/2025
Development of novel malaria pre-erythrocytic vaccine antigens targeting Plasmodium sporozoite liver infection
Objectives
This proposal aims:
- to identify PLS protein epitopes that function in hepatocyte recognition, for use as a vaccine antigen; and
- 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.
Previously, using a phage peptide display library, this research group had identified Plasmodium parasite ligands and corresponding host cell receptors important for sporozoite-Kupffer cell interaction in the mammalian liver. Using a similar approach, the HP1 peptide was identified, 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, Plasmodium Phospholipid Scramblase (PLS) was identified as the sporozoite ligand of hepatocytes and a potential vaccine antigen. It is expected that this approach will lead to enhancement of the moderate protective efficacy of the most advanced RTS,S/AS01 malaria vaccine.
Jan 2023 — Dec 2025
$392,412
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