Identification of cross-stage, cross-species malaria CD8+ T cell antigens

Key Points:

• The World Health Organization's 2025 World Malaria Report highlights the growing threat of antimalarial drug resistance, emphasizing the urgent need for new strategies in malaria control and treatment.
• Recent research has advanced understanding of Plasmodium vivax biology, including its erythrocyte tropism, transcriptomic profiles at various life stages, and immune evasion mechanisms, which are critical for vaccine development.
• Novel malaria vaccines such as RTS,S/AS01 and R21/Matrix-M show promise in inducing protective immunity in children, though challenges remain regarding the duration of efficacy and the impact of malaria exposure on immune responses.
• Cutting-edge immunopeptidomics and mass spectrometry techniques have identified specific Plasmodium-derived peptides presented by MHC molecules, facilitating the discovery of new T cell epitopes and informing design of next-generation vaccines targeting both liver and blood stages.
• Studies employing humanized mouse models and nonhuman primates have provided valuable insights into Plasmodium liver stage development and host immune responses, supporting translational research aimed at achieving sterile immunity through sporozoite-based vaccine approaches.