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The Plasmodium vivax circumsporozoite protein (PvCSP) is the most abundant surface protein on the sporozoite stage of the P. vivax parasite, which is responsible for a significant portion of global malaria cases. PvCSP is essential for the parasite's life cycle, mediating sporozoite development in the mosquito vector and facilitating the invasion of human hepatocytes by binding to heparan sulfate proteoglycans [1, 5, 9]. Structurally, the protein consists of a central repeat region containing immunodominant B-cell epitopes, flanked by conserved N-terminal and C-terminal domains [2, 3, 8]. It is a primary target for pre-erythrocytic vaccine development, with the goal of eliciting antibodies that neutralize sporozoites before they can infect the liver and form dormant hypnozoites [1, 13]. However, vaccine efficacy is challenged by the high degree of allelic diversity in the central repeat region, which includes the VK210, VK247, and P. vivax-like variants [3, 7, 11]. While candidates like VMP001 have demonstrated immunogenicity and the ability to delay parasitemia in clinical trials, achieving consistent sterile protection remains a major therapeutic challenge [6, 14].
Induction of neutralizing antibodies and T-cell responses to block sporozoite invasion of host hepatocytes.
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