Vaccines address public health issues ranging from pandemic outbreaks to childhood disease. Despite this diversity, molecular approaches are beginning to find broad application. This Keystone Symposia conference seeks to bring together antibody aficionados, B cell immunologists, structural biologists, and vaccine developers from government, academia, biotechnology, and major pharmaceutical companies to review the utility of structure-based vaccine design and antibody-based immune monitoring, and in doing so hope to transform standard approaches of vaccine development. This meeting aims (1) to provide examples of the ”antibody-to-vaccine” paradigm for RSV, CMV and other pathogens that have resisted standard vaccinology; (2) to describe procedures whereby B cells can be taught to make the right antibodies; (3) to describe molecular approaches for vaccine improvement; and (4) to discuss how molecular approaches can be used to speed development (as may be needed, for example, in the case of pandemics) and to reduce developmental and regulatory costs (for vaccines in general and in particular to enable provision to the developing world). Overall, we seek to integrate molecular approaches for vaccine development and read-out with other transformative advances including mRNA delivery, next-generation sequencing of B cell transcripts, and control of B cell-T cell interactions. This conference will be held jointly with a Keystone Symposia conference on B Cell-T Cell Interactions and several shared sessions will highlight synergistic areas of research between these communities.