Animal study demonstrates that mRNA-encoded virus-like particles protect mice against Plasmodium vivax malaria, indicating a viable pre-erythrocytic vaccine platform.
mRNA platforms have been proposed for delivery of malaria vaccine candidates capable of inducing protective immunity. Here, we demonstrate that mammalian cells transfected in vitro with mRNA constructs encoding regions of Plasmodium vivax circumsporozoite protein (PvCSP) fused to hepatitis B surface antigen (HBsAg) secrete virus-like particles (VLPs). Immunization of mice with such mRNA constructs elicits PvCSP-specific immune responses that confer significant protection against challenge with transgenic P. berghei sporozoites expressing PvCSP. Feature selection and regression analyses identified immune correlates associated with protection. These include IgG2b titers, IgA levels, and presence of IgGs targeting PvCSP tandem repeat vk210. These findings establish mRNA-delivered PvCSP-HBsAg VLPs as a viable strategy for development of a P. vivax pre-erythrocytic stage vaccine and provide insights into immune correlates of protection.
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Martinez et al. (2026) studied this question.
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