Serine repeat antigen 5 (SERA5) (SERA5)

Serine repeat antigen 5 (SERA5) is a highly abundant soluble protein secreted into the parasitophorous vacuole of Plasmodium falciparum during the blood stage of malaria infection (Miller et al., 2002). Although it belongs to the papain-like cysteine protease family, SERA5 is unusual because it contains a serine residue instead of a cysteine at its active site, functioning as a serine protease (Hodder et al., 2003). It plays a critical role in the egress of merozoites from host erythrocytes by facilitating the rupture of the parasitophorous vacuole membrane (PVM) and the red blood cell membrane (Collins et al., 2017). This egress step is vital for the release of merozoites and the subsequent invasion of new erythrocytes, making SERA5 an essential protein for parasite survival (UniProt P69193). Due to its essentiality and high expression levels, SERA5 is a primary target for antimalarial drug development and vaccine design (Palacpac et al., 2011). The vaccine candidate BK-SE36, based on a conserved N-terminal domain of SERA5, has shown promise in clinical trials by inducing protective antibodies that inhibit parasite growth (Tougan et al., 2013). Targeting SERA5 offers a strategy to block the spread of infection within the host by trapping the parasite within the spent erythrocyte. Challenges in targeting SERA5 include the high degree of genetic polymorphism found in certain regions of the gene, which can lead to immune evasion (Tougan et al., 2013).

Other names

SERA-5p126SERPp140Serine-repeat protein 5Serine repeat antigen protein 5126 kDa soluble antigen

Inhibition of SERA5 protease activity or blocking its processing prevents the rupture of the parasitophorous vacuole membrane, thereby inhibiting the egress of merozoites from infected erythrocytes and halting the parasite life cycle.