Non-CSP Plasmodium falciparum sporozoite surface and liver-stage membrane proteins (Non-CSP antigens)

Non-CSP Plasmodium falciparum sporozoite surface and liver-stage membrane proteins represent a diverse group of antigens essential for the pre-erythrocytic phase of malaria infection. While the Circumsporozoite Protein (CSP) is the primary target of current vaccines, these non-CSP proteins, including Thrombospondin-related anonymous protein (TRAP), Cell-traversal protein for ookinetes and sporozoites (CelTOS), and the P52/P36 complex, are critical for parasite motility, host cell traversal, and hepatocyte invasion (Duffy et al., 2021, Nature). These proteins are expressed either on the surface of the sporozoite as it migrates from the mosquito bite site to the liver or on the membrane of the parasite during its development within hepatocytes (Sack et al., 2017, Vaccine). Therapeutic strategies targeting these molecules include viral-vectored vaccines designed to elicit potent T-cell responses and monoclonal antibodies aimed at neutralizing sporozoite infectivity (Tine et al., 2011, PLoS ONE). Because many of these proteins are involved in the gliding machinery or the formation of the parasitophorous vacuole, their inhibition can prevent the establishment of a systemic infection. They are considered vital components for next-generation multi-stage malaria vaccines intended to improve upon the efficacy of CSP-only formulations (Ishino et al., 2004, JEM).

Other names

Minor sporozoite surface proteinsNon-CSP pre-erythrocytic antigensLiver-stage antigens (LSA)Sporozoite microneme proteinsPre-erythrocytic membrane proteins

Inhibition of sporozoite gliding motility, blocking of hepatocyte invasion, and induction of T-cell mediated destruction of infected hepatocytes.