Plasmodium vivax cysteine-rich protective antigen (PvCyRPA), an important element for vaccine strategies targeting P. vivax, interacts with human erythrocyte surface.

Plasmodium vivax is one of the six species of the Plasmodium genus causing malaria in humans; furthermore, it is the species having the widest worldwide distribution. Despite causing a substantial health burden, progress in developing targeted interventions against P. vivax has been hampered by limited knowledge regarding its biology and antigen repertoire. The cysteine-rich protective antigen (CyRPA) has been identified as a key antigen concerning Plasmodium parasites. CyRPA is a highly conserved Plasmodium spp. protein which is essential for P. falciparum erythrocyte invasion via its role in a multiprotein complex; however, its function in P. vivax remains poorly understood. This study has investigated PvCyRPA expression, localisation, and functional role. It demonstrates that the pvcyrpa gene is transcribed and translated into late P. vivax VCG-1 strain schizonts, its subcellular location suggests membrane association. Recombinant PvCyRPA produced in baculovirus and COS-7 systems binds to both CD71+ reticulocytes and normocytes, highlighting its role in erythrocyte interaction; >90 % of tested sera from malaria-exposed individuals recognised this protein, thus confirming its strong antigenicity. Such findings have provided the first evidence of PvCyRPA's functional relevance regarding P. vivax and support its potential as a vaccine candidate. Future studies should be focused on identifying its receptor(s) and minimal interaction regions critical for host-parasite binding, thereby paving the way for multi-antigen, anti-P. vivax vaccine strategies.