Developmental Biology of Sporozoite-Host Interactions in Plasmodium falciparum Malaria: Implications for Vaccine Design

Abstract

SUMMARY The Plasmodium falciparum sporozoite infects different types of cells in a mosquito's salivary glands and human epithelial and Kuppfer cells and hepatocytes. These become differentiated later on, transforming themselves into the invasive red blood cell form, the merozoite. The ability of sporozoites to interact with different types of cells requires a wide variety of mechanisms allowing them to survive in both hosts: mobility, receptor-ligand interactions with different cellular receptors, and transformation and development into other invasive parasite forms, which are vitally important for parasite survival. Sporozoite complexity is reflected in the large quantity of proteins that can be expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP, LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in infection and their potential use as vaccines. Our work has been focused on the search for the molecular mechanisms of parasite-host cellular receptor-ligand interactions by identifying amino acid sequences and the critical binding residues from these proteins relevant to parasite invasion. Once such sequences have been identified, it will be possible to modify them to induce a strong immune response against P. falciparum in the experimental Aotus monkey model. This all leads towards developing multistage, multicomponent, subunit-based vaccines that will be effective in eradicating or controlling malaria caused by P. falciparum .