The rapid genetic evolution of pathogenic viruses, such as SARS-CoV-2 and influenza, alongside the absence of effective vaccines for many infectious diseases such as HIV and Zika, entails continuous efforts to develop highly effective vaccines to control their transmission. Conventional DNA vaccines are associated with insertional mutagenesis and other toxic effects. High-profile mRNA vaccines currently in use require long-term cold-chain storage and frequent booster vaccinations. In contrast, subunit vaccines, which are based on proteins derived from pathogens to trigger protective immune responses, offer a favorable safety profile and require mild storage conditions. However, subunit vaccines are typically less immunogenic than whole cell-based vaccines. As such, the combined use of adjuvants and subunit vaccines has continued for many decades. Nonetheless, clinically available adjuvants essential to boost vaccine efficacy with good safety profiles are still very limited. One reason for this is that adjuvants are not effectively localized with protein antigens upon administration, leading to undesirable systemic activation of the immune system. To address this challenge, we developed an innovative self-adjuvanting subunit nanovaccine based on C7A ((2-Hexamethyleneimino)ethyl methacrylate) through free radical polymerization. In so doing we demonstrated its capacity to enhance lymph node transportation and antigen cross-presentation, increase antibody production and cytokine secretion, and promote the maturation of B and T cells in germinal centers. Building on this foundation, this protocol seeks to develop a next-generation subunit vaccine delivery system that elicits advantageous adaptive immune responses with minimal number of doses. Specifically, we will (Aim 1) seek to modify and optimize the existing formulation, loaded with SARS-CoV-2 antigen as an example; (Aim 2) conduct comprehensive in vivo valuations to assess performance. This work has the potential to serve as a platform technology for the delivery of a litany of additional protein antigens against various infectious diseases.