Enabling global access to potent subunit vaccines with a simple and scalable injectable hydrogel platform

Vaccines have been crucial to dramatic improvements in global health in recent decades, yet next-generation vaccine technologies remain out of reach for much of the world. In particular, there are two overarching global needs: (i) develop vaccines eliciting more potent and durable immune responses, especially to reduce incidence of highly communicable diseases, and (ii) enable simple and cost-efficient formulation to maximize global access. Here, we develop an injectable hydrogel depot technology prepared through physical mixing of commercially available, generally recognized as safe (GRAS) polymers that can be formulated with subunit vaccine components to improve immune responses compared to standard vaccine formulations. We demonstrate that these hydrogels are shear-thinning and rapidly self-healing, enabling facile administration <i>via</i> injection, and they exhibit high yield stresses required for robust <i>in vivo</i> depot formation post-injection. These rheological properties prolong release of subunit vaccine cargo over a period of weeks, both <i>in vitro</i> and <i>in vivo</i>, and synchronize release kinetics across physicochemically distinct vaccine components (antigens and adjuvants). When used for formulation of subunit vaccines against wild-type SARS-CoV-2 and H5N1 influenza, these hydrogels enhance potency and durability of immune responses. This vaccine formulation technology can improve protection against current and potential future pandemic pathogens.