Vaccination with Engineered Protein-Glyco-Adjuvant Conjugates to Induce Robust and Durable Immune Responses in Cancer and Infectious Disease

The development of new prophylactic and therapeutic vaccines is challenging due to a lack of strong, clinically approved adjuvants. To address this challenge, we have created a modular vaccine platform, consisting of a mannosylated TLR7-agonizing polymer, p(Man-TLR7), conjugated to a protein, which can have different functionalities depending on the context. Here, we investigate the efficacy of this vaccine platform both as a therapeutic cancer vaccine and as a prophylactic COVID-19 vaccine. In the context of cancer, we observe a therapeutic benefit in multiple cold tumor models when p(Man-TLR7) is targeted to the tumor extracellular matrix via conjugation to various targeting proteins. This therapeutic benefit is accompanied by an increase in the proportion of CD8+ effector cells in the tumor, as well as an increase in the proportion of activated cross-presenting CD103+ DCs in the tumor. In the context of COVID-19, p(Man-TLR7), when conjugated to SARS-CoV-2 antigens, induces high titers of neutralizing antibodies, as well as robust antigen-specific T cell responses. Overall, our results demonstrate the adaptability and broad clinical translational potential of our engineered protein-glyco-adjuvant vaccine platform.