Continuing investments in vaccine innovation are insufficiently translated into market entries of novel vaccines. This innovation paradox is in part caused by stakeholders lacking complete understanding of the complex array of steps necessary for vaccine development and collaboration difficulties between the wide variety of stakeholders involved. Models providing cross-domain understanding can improve collaboration but currently lack both comprehensibility and granularity to enable a prioritized view of activities and criteria. Key opinion leaders (KOLs) were asked to contribute to the definition of a vaccine innovation cycle (VIC). In a first step, 18 KOLs were interviewed on the stages (activities and results) and gates (evaluation criteria and outcomes) of vaccine innovation. This first description of the VIC was subsequently validated and refined through a survey among 46 additional KOLs. The VIC identifies 29 distinct stages and 28 corresponding gates, distributed in ten different but integrated workstreams, and comprehensibly depicted in a circular innovation model. Some stage-gates occur at defined moments, whereas the occurrence and timing of other stage-gates is contingent on a variety of contextual factors. Yet other stage-gates continuously monitor internal and external developments. A gap-overlap analysis of stage-gate criteria demonstrated that 5 out of 11 criteria employed by vaccine developers correspond with criteria employed by competent (regulatory) authorities. The VIC provides a comprehensive overview of stage-gates throughout the value chain of vaccine innovation. Its cyclical nature highlights the importance of synchronizing with unmet needs and market changes, and conceptualizes the difference between incremental and radical vaccine innovation. Knowledge on the gap between internal and external criteria will enhance the viability of newcomers to the field. The VIC can be used by stakeholders to improve understanding and communication in forming collaborative alliances and consortia. Such a boundary-spanning function may contribute to the reduction of process inefficiencies, especially in public-private partnerships.