Shaping immunity against infectious diseases with multivalent DNA vaccines

Immunization has dramatically transformed human and animal health. Since its earliest days, vaccination has served as a fundamental strategy for infectious disease prevention, providing population-level coverage for childhood diseases and seasonal infections, and serving as a rapid response to pandemic pathogens. Yet, there is continued circulation of endemic, emerging, and reemerging pathogens for which there are no licensed prophylactic measures. The successes of nucleic acid technologies during the COVID-19 pandemic, exemplified in the first two licensed mRNA vaccines [1] and the first DNA vaccine receiving emergency use authorization for human use [2], are reinvigorating vaccine development to tackle this urgent unmet need. The inherent stability of DNA offers advantageous features such as thermostability and extended shelf life. These characteristics are pivotal for transport and storage in resource-constrained environments, like low and middle-income countries. Furthermore, the ability to encode large transgenes and well-established modular assembly pipelines are key attributes of DNA-based platforms. This versatility extends to combination strategies of individual DNA vaccines as a multivalent drug product. Multivalent synthetic DNA vaccines are therefore emerging as part of the exciting nucleic acid-based vaccine landscape as a strategy to induce robust and durable immunity in diverse global populations.