Design for Manufacturability (DFM) is a common practice in many industries to reduce inefficiency in scaling production, lower costs, and improve time to market. Vaccine design, in contrast, has predominantly relied on whatever nature provides. With advances in systems biology and genome engineering, there is an opportunity to rethink how we design subunit vaccines with the end in mind, and simplify production processes, improve yields, and lower cost of goods manufactured. This talk will spotlight three vignettes that show how upfront molecular and cell engineering can make vaccine candidates that are more manufacturable while retaining immunogenicity. First, we’ll explore a trivalent rotavirus subunit vaccine where vector engineering and conservative sequence changes reduced the number of operations by more than 50% and enabled a consolidated single production process for the trivalent vaccine. Next, we’ll look at how historical sequence analyses and rational engineering optimized the production of a SARS‐CoV-2 receptor-binding domain by 100x compared to the ancestral sequence, but also unexpectedly broadened neutralizing responses across emerging variants. Finally, we’ll consider how to modularize the production of virus-like particles (VLPs) in a way that allows tunable modularity and is amenable to low-cost platform continuous production. Together, these examples demonstrate how incorporating DFM in vaccine discovery could transform their development to enable lower costs and improved products amenable to state-of-the-art manufacturing to improve the affordability and availability of these products.
