For many life-threatening global infectious diseases effective vaccinations are still lacking. There are numerous challenges in understanding disease transmission, pathology and developing new vaccines, including a limited understanding of immune correlates of protection, identification of viable vaccine candidates, and off-target effects that must be evaluated in staged clinical trials. To generate these antibodies, B cells are activated by T cells to form germinal centers, which are sub-anatomical structures in the B cell follicles of lymph nodes. In germinal centers, B cells rapidly proliferate and mutate to form somatically mutated high-affinity antibody secreting cells. In this talk, I will discuss my laboratory’s effort in developing ex vivo immune organoids using cells from both young and aged individuals to generate antibody secreting cells in a dish or as organ-on-chip against viral infections and antibiotic-resistant bacteria. We further elucidate the role of epigenetic modifiers, such as EZH2, in these responses. Finally, I will discuss development of nanoscale technologies to modulate the differentiation trajectories of T cells against infectious diseases.