• EVI

Novel blood-stage malaria vaccine candidate, adjuvanted PfRipr5, to reach over 50% in vitro efficacy

Plasmodium falciparum is a highly complex pathogen that causes malaria. Protective malaria vaccine approaches can target three development stages of the malaria parasite namely (1) pre-erythrocytic stage to prevent infection of the liver and development into subsequent clinically relevant blood-stage, (2) the asexual blood-stage to prevent multiplication and clinical disease and (3) transmission stage. Last year, the World Health Organization (WHO) recommended the use of RTS,S/AS01, a pre-erythrocytic vaccine however with modest efficacy against clinical malaria that wanes rapidly. To maintain blood-stage immunity, an asexual blood-stage vaccine is considered an important addition to a pre-erythrocytic vaccine. High polymorphism levels in P. falciparum asexual blood-stage malaria vaccine antigens often result in strain-specific immunity that hampers vaccine efficacy.

Developing vaccines based on conserved antigens across multiple strains could be an approach to attain high protective efficacy. The PfRipr/PfCYRPA/Rh5 protein complex is considered to play a central role in the parasite’s invasion mechanism. All three subunits of the protein complex are considered highly conserved across malaria strains and naturally acquired antibody responses in humans are associated with clinical protection against malaria. To develop an improved next-generation asexual blood-stage malaria vaccine targeting the PfRipr/PfCyRPA/Rh5 complex, PfRipr is one of the promising antigens.

In a recent study by partners in EVI-led and GHIT-funded project PfRipr5, this antigen has shown to be a promising vaccine candidate against malaria when formulated with adjuvants for human use.

The study aimed to evaluate the immunogenicity of PfRipr5 formulated with different adjuvants in rabbits, as well as to test the anti-malaria efficacy of the antibodies in vitro. Firstly, expression of the PfRipr5 antigen was tested both in mammalian and insect cells. The produced proteins were further characterised, and the optimal production and purification conditions were identified. Rabbits were immunised with the PfRipr5 alone or formulated with Alhydrogel®, GLA-SE or CAF®01 adjuvants. The level of antibodies produced in rabbits following immunisation was measured by ELISA and their efficacy against parasite proliferation was assessed in vitro, using a growth inhibition assay (GIA).

Among the formulations tested, the highest growth inhibition assay activity was attained with antibodies induced by immunisation with PfRipr5 formulated with CAF®01 with a mean GIA activity of 57%. Even though it is often difficult to predict efficacy in humans from animal experiments, the fact that PfRipr5/CAF®01 formulation has the potential to induce potent inhibitory antibodies in rabbits supports further pre-clinical and clinical studies with this promising formulation.

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