An mRNA-lipid nanoparticle vaccine targeting the Plasmodium vivax E140 antigen.

Plasmodium vivax (Pv) remains the primary cause of malaria outside Africa, yet no licensed vaccine is available against this pathogen. Here, we evaluate the immunogenicity and protective efficacy of novel vaccines targeting E140, a recently identified multi-stage antigen conserved across Plasmodium species. Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines against P. berghei E140 (PbE140) and P. vivax E140 (PvE140) induced robust antigen-specific IgG antibody responses, germinal center B cell, and long-lived plasma cell responses. Vaccination with PbE140 mRNA-LNP resulted in reduced parasitemia and improved survival in pathogen-challenged mice. Importantly, antibodies elicited by PvE140 mRNA-LNP in mice reduced invasion of primary human reticulocytes by P. vivax merozoites by 56%-78% in ex vivo functional assays. These findings suggest that E140 may be a promising antigen candidate for next-generation vaccines against P. vivax.