Engineered migrasomes provide a robust and thermally stable vaccination platform.

The growing ability of pathogens and tumor cells to evade immune surveillance underscores the urgent need for new vaccine platforms that harness diverse biological mechanisms. Logistical constraints associated with cold-chain transport further limit vaccine accessibility, particularly in resource-limited settings. Migrasomes-specialized organelles produced during cell migration-are inherently stable and enriched with immune-modulating molecules. To overcome the low yield of natural migrasomes, we engineered migrasome-like vesicles (eMigrasomes) using hypotonic shock combined with cytoskeletal disruption to promote vesicle formation. eMigrasome biogenesis depends on core migrasome machinery and recapitulates the biophysical and molecular features of native migrasomes while achieving higher production efficiency. In murine models, eMigrasomes loaded with a model antigen elicited potent antibody responses and retained structural integrity and immunogenicity at room temperature. Moreover, eMigrasomes displaying the SARS-CoV-2 Spike protein induced strong humoral responses and conferred protection against viral challenge in mice. These results establish eMigrasomes as an innovative, thermally stable, and broadly applicable vaccine platform derived from migrasome biology.