A Self‐Adjuvanting Large Pore 2D Covalent Organic Framework as a Vaccine Platform

Abstract Vaccines are one of the greatest human achievements in public health, as they help prevent the spread of diseases, reduce illness and death rates, saving thousands of lives with few side effects. Traditional vaccine development is centered around using live attenuated or inactivated pathogens, which is expensive and has resulted in vaccine‐associated illnesses. Advancements have led to the development of safer subunit vaccines, which contain recombinant proteins isolated from pathogens. Their short half‐life and small size make most subunit vaccines less immunogenic. Here, we introduce a large pore 2D covalent organic framework (COF), PyCOFamide, as a promising solution for an effective subunit platform. Our study demonstrates that simple adsorption of a model antigen, ovalbumin (OVA), onto PyCOFamide (OVA@COF) significantly enhances humoral and cell‐mediated immune response compared to free OVA. OVA@COF exhibited heightened immune cell activation and acts as an antigen reservoir, facilitating antigen‐presenting cell trafficking to the draining lymph nodes, amplifying the humoral immune response. Additionally, the breakdown of the COF releases monomers that adjuvant the activation of immune cells vital to creating strong immunity. This platform offers a potential avenue for safer, more effective subunit vaccines.