Reverse vaccinology focuses on identifying potential vaccine candidates from the perspective of the entire pathogenic genome. In 2000, Rino Rappuoli and colleges first used reverse vaccinology to screen the Group B meningococcus genome and developed the MenB vaccine. With the improvement of sequencing techniques, the integration of organism databases, and the development of many useful bioinformatics tools, reverse vaccinology has been successful in discovering previously unknown antigens and accelerating the development of vaccines. Malaria is a mosquito-borne infectious disease caused by Plasmodium species. Since the parasites have multiple life stages and exhibit various immune evasion strategies, malaria vaccine development remains challenging. We use machine learning to analyze the large genomes of Plasmodium species to explore unknown antigens as potential vaccine candidates.