Malaria is transmitted when infected mosquitos inject Plasmodium sporozoites through the skin of a vertebrate host. Vaccination is the most effective strategy to prevent malaria, but new strategies are needed to improve current pathogen-based vaccines. Immunization against a mosquito saliva protein, AgTRIO, provides protection against Plasmodium infection in mice. In this study, AgTRIO mRNA-lipid nanoparticles were used to generate a robust immune response in mice, resulting in reduced liver infection levels and increased survival when exposed to infected mosquitos. This approach offers advantages over pathogen-based vaccines as the immune response can be boosted with additional mosquito bites.
Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the skin of a vertebrate host. To prevent malaria, vaccination is the most effective strategy and there is an urgent need for new strategies to enhance current pathogen-based vaccines. Active or passive immunization against a mosquito saliva protein, AgTRIO, contributes to protection against Plasmodium infection of mice. In this study, we generated an AgTRIO mRNA-lipid nanoparticle (LNP) and assessed its potential usefulness as a vaccine against malaria. Immunization of mice with an AgTRIO mRNA-LNP generated a robust humoral response, including AgTRIO IgG2a isotype antibodies that have been associated with protection. AgTRIO mRNA-LNP immunized mice exposed to Plasmodium berghei-infected mosquitoes had markedly reduced initial Plasmodium hepatic infection levels and increased survival compared to control mice. In addition, as the humoral response to AgTRIO waned over 6 months, additional mosquito bites boosted the AgTRIO IgG titers, including IgG1 and IgG2a isotypes, which offers a unique advantage compared to pathogen-based vaccines. These data will aid in the generation of future malaria vaccines that may include both pathogen and vector antigens.
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