Metal–Organic\nFramework Encapsulated Whole-Cell\nVaccines Enhance Humoral Immunity against\nBacterial Infection

The\nincreasing rate of resistance of bacterial infection against\nantibiotics requires next generation approaches to fight potential\npandemic spread. The development of vaccines against pathogenic bacteria\nhas been difficult owing, in part, to the genetic diversity of bacteria.\nHence, there are many potential target antigens and little <i>a priori</i> knowledge of which antigen/s will elicit protective\nimmunity. The painstaking process of selecting appropriate antigens\ncould be avoided with whole-cell bacteria; however, whole-cell formulations\ntypically fail to produce long-term and durable immune responses.\nThese complications are one reason why no vaccine against any type\nof pathogenic <i>E. coli</i> has been successfully clinically\ntranslated. As a proof of principle, we demonstrate a method to enhance\nthe immunogenicity of a model pathogenic <i>E. coli</i> strain\nby forming a slow releasing depot. The <i>E. coli</i> strain\nCFT073 was biomimetically mineralized within a metal–organic\nframework (MOF). This process encapsulates the bacteria within 30\nmin in water and at ambient temperatures. Vaccination with this formulation\nsubstantially enhances antibody production and results in significantly\nenhanced survival in a mouse model of bacteremia compared to standard\ninactivated formulations.