Few therapeutic strategies can rival vaccination in terms of effectiveness at treating and preventing infectious diseases. Unfortunately, despite a strong track record of success over the past century for the eradication of numerous lethal and high morbidity human diseases, we still do not have a clear understanding of how the process of vaccination works. As a result, modern vaccines are still developed using costly and time consuming trial and error approaches, and despite years of effort we are currently unable to vaccinate against many of our most serious threats. As immunoengineers, we propose the use of techniques and principles from bioengineering, polymer chemistry, and immunobiology as a multidisciplinary approach to the study of vaccination. We are developing nanomaterial-based vaccines using combinations of diverse adjuvants and antigens, currently with a focus on tuberculosis.