This technology focuses on the creation of single-component AMA1-RON2 (Apical membrane antigen 1-rhoptry neck protein 2) vaccine candidates. These candidates are based on a novel composition of matter designed to elicit a more effective immune response against the malaria parasite Plasmodium falciparum. The standout aspect of this technology is the Structure-Based Design 1 (SBD1) immunogen, engineered through a structure-based design that significantly enhances its ability to produce potent, strain-transcending neutralizing antibodies. This approach not only surpasses the efficacy of traditional AMA1-RON2 complexes and other insertion fusion designs but also boasts higher thermal stability, indicating better preservation and longevity of the vaccine. The technology’s increased stability and efficiency in production present an opportunity to lower vaccine manufacturing costs and simplify logistics, especially in regions where malaria is endemic. Additionally, the adaptability of these immunogens for integration with nanoparticle platforms could further amplify their immunogenicity, paving the way for more robust and lasting protection against malaria. This innovation can potentially transform malaria prevention and control, offering a more effective, stable, and cost-efficient solution to a disease that continues to impact millions worldwide.