Reticulocyte-binding protein homologue 5 (RH5)

Reticulocyte-binding protein homologue 5 (RH5) is an essential, highly conserved protein secreted by the merozoite stage of the malaria parasite Plasmodium falciparum. It forms a critical complex with other parasite proteins to mediate the final, irreversible step of erythrocyte invasion by binding to the human host receptor Basigin (CD147) (Crosnier et al., 2011, Nature). Because RH5 is indispensable for invasion across all tested parasite strains and exhibits limited genetic polymorphism, it is considered a leading candidate for a blood-stage malaria vaccine. The RH5.2-VLP construct is a second-generation vaccine candidate that utilizes a stabilized version of the RH5 protein (RH5.2) displayed on virus-like particles (VLPs), such as those derived from the Acinetobacter phage AP205, to enhance the immune response (Silk et al., 2020, Molecular Therapy). This VLP-based presentation promotes the cross-linking of B-cell receptors, leading to higher titers of neutralizing antibodies compared to monomeric protein vaccines. In clinical development, vaccines targeting RH5 aim to elicit antibodies that block the RH5-Basigin interaction, thereby preventing the parasite from entering red blood cells and effectively neutralizing the infection (Minassian et al., 2021, NPJ Vaccines).

Other names

PfRH5RH5.2RH5.2-VLPReticulocyte-binding protein homolog 5

Induction of neutralizing antibodies that sterically hinder the interaction between the parasite RH5 protein and the human host receptor Basigin (CD147), thereby preventing the invasion of erythrocytes by Plasmodium falciparum merozoites.