The COVID-19 pandemic starkly revealed the profound inequities embedded within the global vaccine ecosystem, where vaccine nationalism by high-income countries left low- and middle-income countries in a state of critical dependency. This chapter argues that the coronavirus crisis was not an isolated rupture but a continuation of a chronic condition long experienced in the Global South. Furthermore, by examining the two sociotechnical imaginaries of C-TAP and ACT-A, this chapter demonstrates how the dominance of the latter enabled the private governance of a public health crisis and reproduced entrenched access inequities. At the same time, the chronicity of crisis in the Global South has also created a normative demand for equitable vaccine access and, necessarily, a new vaccine ecosystem. The chapter posits that the coronavirus crisis created a critical juncture, compelling a fundamental rethinking of the notions of vaccine security and responsibility. As an empirical illustration of such rethinking in practice, this chapter analyses the case of the African Union’s Partnerships for African Vaccine Manufacturing (PAVM). The PAVM, though fraught with challenges and tensions, represents an ambitious, alternative sociotechnical imaginary; a political imperative to assemble a new vaccine ecosystem from the ground up.