RH5-interacting protein (Ripr) (Ripr)

RH5-interacting protein (Ripr) is a 123 kDa cysteine-rich protein of Plasmodium falciparum that is essential for the invasion of human erythrocytes (UniProt: Q8I6U1). It functions as a member of the RH5-CyRPA-Ripr (RCR) complex, which is required for the parasite to commit to host cell entry after initial attachment (Wong et al., 2019, Nature). The C-terminal region of Ripr, which contains several epidermal growth factor (EGF)-like domains, is particularly important as it is the target of potent growth-inhibitory antibodies that prevent the RCR complex from functioning (Chen et al., 2011, PNAS). As a highly conserved antigen across different P. falciparum strains, Ripr is a leading candidate for the development of next-generation blood-stage malaria vaccines (Ragotte et al., 2022, NPJ Vaccines). Therapeutic strategies focus on using monoclonal antibodies or vaccine-induced polyclonal antibodies to disrupt the RCR complex's ability to facilitate membrane fusion or pore formation during invasion. Blocking the C-terminal EGF-like domains specifically has been shown to provide high levels of protection in preclinical models, making it a focal point for structural vaccinology.

Other names

PfRiprP123Reticulocyte-binding protein homolog 5-interacting proteinPF34215c

Antibodies targeting the C-terminal EGF-like domains of Ripr sterically hinder the formation of the RH5-CyRPA-Ripr (RCR) complex or its interaction with the erythrocyte membrane, thereby blocking parasite entry (Wong et al., 2019).