ZWITTERIONIC HYDROGEL DEPOT FOR EXTENDED ANTIGEN AND VACCINE DELIVERY
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United States of America
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Apr 10, 2025
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Oct 7, 2024
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Oct 7, 2024
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Abstract
The subject invention pertains to a long-term antigen depot that can bypass FBR and engage DCs to mature and migrate to lymph nodes to activate antigen-specific T-cell activations. Leveraging on the immunomodulatory properties of exogenous polysaccharides and the anti-fouling characteristics of zwitterionic phosphorylcholine (PC) polymer, the invention features a PC functionalized dextran (PCDX) hydrogel for long-term antigen delivery. PCDX in both injectable scaffold and microparticles (MPs) forms effectively evades FBR and provides slow release of antigens resulting in local enrichment of CD11c+ DCs at the MPs injection sites. DC cultured on PCDX exhibits strong immunogenic activation with high CD86, CD40, MHC-I/peptide complex. PCDX also generates DC with propensity in migration to lymph nodes, as well as antigen presentation to trigger both CD4+ and CD8+ arms of T-cell responses. Besides cellular responses, PCDX can also induce potent humoral responses, with high levels of antigen specific IgG1 and IgG2a by day 28. Overall, PCDX provides long-term delivery of antigens for vaccine development.
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