Exploiting aluminum-based metal-organic frameworks as dual-adjuvant delivery platforms for potentiated immune response of subunit vaccines

As a promising class of vaccines, the primary challenge in subunit vaccines development is effectively inducing robust cellular immune responses against pathogens. Existing adjuvants and delivery systems, whether clinically approved or under development, continue to face significant limitations. Herein, we prepared nanovaccines by binding antigens to aluminum-based metal–organic frameworks (MOFs) via responsive linkers and incorporating CpG oligodeoxynucleotides. Within nanovaccines, the granulation and stimuli-responsive release of soluble antigens optimizes antigen utilization. The presence of aluminum ions and organic ligands within the carriers, in conjunction with adsorbed CpG adjuvants, synergistically enhances immune responses. Notably, the inherent properties of the MOFs carriers allow for prolonged retention of nanovaccines at the injection site post-vaccination, enabling sustained antigen stimulation conducive to establishing enduring immune memory. Furthermore, the carriers demonstrate broad adaptability across various antigens, displaying their universal adaptability. Overall, this work offers a promising vaccine preparation method characterized by safety, efficacy, simplicity, and potential for clinical translation.