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Plasmodium falciparum Circumsporozoite Protein (CSP) and Thrombospondin-Related Adhesion Protein (TRAP) are essential surface antigens of the malaria parasite during its pre-erythrocytic stage. CSP is the dominant surface protein on sporozoites and is critical for parasite maturation and hepatocyte recognition (UniProt P19598). TRAP is a transmembrane protein necessary for gliding motility and host cell invasion; it is frequently used in vaccine development as a Multi-Epitope (ME-TRAP) construct to broaden T-cell recognition (PubMed: 23900242). These antigens are the primary components of leading malaria vaccines, including RTS,S/AS01 and R21/Matrix-M, which function by inducing neutralizing antibodies and cellular immunity to prevent the parasite from establishing a liver-stage infection (WHO, 2023). Targeting these proteins aims to block the life cycle of P. falciparum before the onset of clinical symptoms associated with the blood stage. However, the high genetic diversity of these antigens and the need for sustained high antibody titers present significant hurdles for long-term vaccine efficacy (PubMed: 34614398).
Induction of high-titer neutralizing antibodies against the CSP repeat region to block sporozoite invasion of hepatocytes, combined with the stimulation of CD4+ and CD8+ T-cell responses against TRAP-expressing liver-stage parasites to eliminate infected cells (WHO, 2023; Nature Communications, 2013).
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