The Plasmodium vivax high molecular weight (HMW) rhoptry 3 protein (RhopH3) is involved in human red blood cell binding.

Plasmodium vivax represents a significant challenge regarding malaria eradication efforts due to its biological peculiarities, its wide geographical distribution and experimental tools' limited availability. No anti-P. vivax vaccine has been approved and, unlike the scenario concerning Plasmodium falciparum, only a limited number of antigens having been evaluated. This study has thus been aimed characterising the P. vivax RhopH3 protein, evaluating its genetic diversity, natural selection, ability to bind to human erythrocytes and antigenicity. Three regions (R1, R2 and R3) were identified, based on sequence conservation and selection signals; these were cloned and expressed in two expression systems for functional analysis. Immunoprecipitation and rosette-formation assays highlighted R1 and R3 regions' erythrocyte binding capability, R1 having the highest binding rates. Antigenicity results revealed naturally infected patient sera's low reactivity against R1 and R3, thereby agreeing with previous reports regarding apical organelle-located proteins, such as PfRhopH3. The results thus suggested that PvRhopH3 is a conserved protein having erythrocyte-binding capacity and low natural antigenicity, such properties which could be exploited and optimised for designing P. vivax control strategies.