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Vaccines induce specific immunity through antigen uptake and processing. However, while nanoparticle vaccines have elevated uptake, the impact of intracellular protein release and how this affects processing and downstream responses are not fully understood. Herein, we reveal how tuning unmodified antigen release rate, specifically through modulation of metal–organic framework (MOF) pore size, influences the type and extent of raised adaptive immunity. We use two MOFs in the NU-100x series with 1.4 nm difference in pore diameter, employ facile postsynthesis loading to achieve significant internalization of model protein antigen ovalbumin (ca.1.4 mg/mg), and observe distinct antigen release and intracellular processing profiles influenced by MOF pore size. We investigate how this difference in release biases downstream CD8⁺, T_H1, and T_H2 T cell responses. Ovalbumin-loaded NU-1003 induced 1.8-fold higher CD8⁺:CD4⁺T cell proliferation ratio and displayed 2.2-fold greater ratio of CD4⁺T_H1:T_H2 cytokines compared to ovalbumin-loaded NU-1000. Antigen released from NU-1000 in vivo exhibited stronger antigen-specific IgG responses, which is dependent on CD4⁺T cells (up to ninefold stronger long-term antibody production and 5.9-fold higher IgG1:IgG2a ratio), compared to NU-1003. When translated to wild-type SARS-CoV-2 receptor-binding domain (RBD) protein, RBD-loaded NU-1000 induced 60.5-fold higher IgG1:IgG2a compared to NU-1003. Wild-type RBD-loaded NU-1000 immunization also induced a greater breadth of epitope recognition compared to NU-1003, as evidenced by increased binding antibodies to the Omicron RBD variant. Overall, this work highlights how antigen release significantly influences immunity induced by vaccines and offers a path to employ unmodified antigen release kinetics to drive personalized protective responses. 

Abstract Global reliance on fossil fuel combustion for energy production has contributed to the rising concentration of atmospheric CO₂, creating significant global climate challenges. In this regard, direct air capture (DAC) of CO₂from the atmosphere has emerged as one of the most promising strategies to counteract the harmful effects on the environment, and the further development and commercialization of this technology will play a pivotal role in achieving the goal of net‐zero emissions by 2050. Among various DAC adsorbents, metal–organic frameworks (MOFs) show great potential due to their high porosity and ability to reversibly adsorb CO₂at low concentrations. However, the adsorption efficiency and cost‐effectiveness of these materials must be improved to be widely deployed as DAC sorbents. To that end, this perspective provides a critical discussion on several types of benchmark MOFs that have demonstrated high CO₂capture capacities, including an assessment of their stability, CO₂capture mechanism, capture‐release cycling behavior, and scale‐up synthesis. It then concludes by highlighting limitations that must be addressed for these MOFs to go from the research laboratory to implementation in DAC devices on a global scale so they can effectively mitigate climate change.