Immunization remains one of the most effective preventive public health measures, the indirect effects of which are considered a global public good with an impressive net return over costs. Vaccines have contributed to “final public good”: eradication of two viruses and regional elimination of a half dozen or more other pathogens. The development of new vaccines, therefore, would seem an obvious priority area for use-inspired and applied biomedical research, yet the endeavor has become increasingly more challenging. The “easy vaccines have been made” belief, crowded vaccine schedules, escalating costs of full vaccination programs (particularly in cost-sensitive Gavi-eligible countries), and platforms for maternal immunization and Public Health Emergencies of International Concern have all contributed to an urgent need for new or improved approaches to the discovery, development and delivery of vaccines, particularly those that are cheaper, simpler to manufacture, and more convenient to use. The aim of this symposium is to provide a comprehensive survey of emerging tools from the most upstream antigen/vaccine discovery, to active and passive immunization platforms, clinical trials, and manufacturing, formulation and delivery, the desired outcome of which is to provide a forum for an integrated discussion on how best to meet the increasing challenges faced by the scientific community’s efforts in new vaccine development. The Keystone Symposia conference has been specifically paired with the conference on “HIV Vaccines” since discovering, developing and delivering an effective HIV vaccine may be one that benefits most from novel technologies, including new tools in structural immunology and interrogating human immune responses.