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Asexual blood-stage malaria vaccine candidate PfRipr5: enhanced production in insect cells

05 July 2022

Malaria is a potentially fatal disease caused by parasites transferred to humans through the bites of infected female Anopheles mosquitos. It is both preventable and treatable. There were an estimated 241 million cases of malaria worldwide in year 2020, causing over 627 000 deaths. Children under the age of five accounted for around 80% of all malaria deaths in the African Region. It bears a disproportionately large share of the global malaria burden accounted for 95% of malaria cases and 96% of malaria deaths.

The development of a highly efficient malaria vaccine is critical for disease control and eventual elimination. Currently, only the RTS, S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO for wider use but shows only modest efficacy (Vogel, 2021). Recently, a heterotrimeric protein complex consisting of three highly conserved proteins (PfRh5, PfRipr, and CyRPA) was identified from P. falciparum merozoites as necessary to invade erythrocytes (Volz et al., 2016; Wong et al., 2019) presenting a promising vaccine target (Ragotte et al., 2020). Insect (High Five and Sf9) cells were identified as a better host for PfRipr5 expression than human (HEK293) cells. An optimised process for the development of PfRipr5 malaria vaccine candidate has been developed using cell-baculovirus expression vector system (IC-BEVS). Purified PfRipr5 derived from insect cells presented high purity and strong binding to anti-PfRipr monoclonal antibody (mAb) 29B11, an antibody used as a proxy for confirming the protein’s biological activity.

This is the first report of an asexual blood-stage malaria vaccine candidate based on PfRipr produced using the insect Sf9 and High Five cell lines, highlighting the potential of insect cells to produce it and the importance of optimising the expression vector and culture conditions to boost the expression of secreted proteins.

The malaria asexual blood-stage antigen PfRipr and its most immunogenic fragment PfRipr5 has emerged as promising vaccine candidate. Insect cells have supplied the production of numerous vaccine antigens in a fast and cost-effective manner. Improving this platform further could prove key to its wider use.

This work has been supported by Japan-based Global Health Innovative Technology (GHIT) Fund grant ID: T2018-151.

Image source: Centers for Disease Control and Prevention. Photomicrograph of a blood smear reveals an elongated, cigar-shaped, Plasmodium falciparum parasitic macrogametocyte


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