Nanoparticulate delivery platforms have shown promising advantages for vaccines in many aspects. However, their application was limited so far by lengthy synthetic protocols, the requirement of specific modification of antigen, and by the low efficiency in inducing antigen‐specific cytotoxic T‐lymphocyte responses. This study demonstrates for the first time the construction of metal‐organic‐framework (MOF) based vaccines by encapsulating ovalbumin (OVA) and attaching the cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) in/on zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles. The pH responsive decomposition feature enables the system to release the protein antigens and CpG ODNs in the same antigen presenting cells more efficiently. More importantly, in addition to the induction of a potent immune memory response, both in vitro and in vivo experiments show that the vaccines can induce strong humoral and cellular immunity. These findings suggest that the MOF‐based vaccine platforms can be used to produce effective vaccines against a range of ailments, which will facilitate the application of MOFs in biomedical areas.

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