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The time required to launch new global health vaccines is too long and the late failure rate is unsustainably high. Key barriers include insufficient diversity and quality of preclinical concepts and candidates, immunobiological ignorance, and a lack of understanding of correlates or mechanisms of protection. Root causes include siloed science and linear thinking; poor integration across the discovery/development/delivery ecosystem; and slow entry and limited throughput in early human proof of concept testing. This Keystone Symposia meeting aims to bring together those pioneering novel, creative solutions to these problems of global vaccine discovery and development across the academic/biotech/product development partner/pharma spectrum.