Hierarchically assembled hydrogels can act as drug delivery platforms to enhance the body’s immune response to difficult vaccine candidates by precisely controlling the timing and location of vaccine exposure within the body. Tuning of hydrogel dynamic structural and mechanical characteristics allows coordination of cargo spatial and temporal exposure and immune cell interaction. We have designed an injectable and self-healing supramolecular polymer-nanoparticle (PNP) hydrogel that can be tuned to slowly release vaccine cargos into the body, enabling a more potent, durable, and high-quality immune response. The PNP hydrogel is formed by dynamic noncovalent interactions between PEG-b-PLA nanoparticles and dodecyl-modified hydroxypropyl methylcellulose polymers. Adjusting hydrogel formulation affects the diffusion and dynamic mesh size of the polymer network, affording precise control over the encapsulation and release of molecular cargo. In this presentation we will discuss the development of PNP materials, the dependence of cargo diffusivity on hydrogel composition, and the influence of cargo release on vaccine efficacy. We will describe the use of PNP hydrogels for sustained delivery of a subunit influenza vaccine comprises components of varying molecular weight and chemical composition. We show how the dynamic physical characteristics of the PNP hydrogels enable physicochemically distinct influenza hemagglutinin antigen and a toll-like receptor 7/8 agonist adjuvant to be co-delivered over prolonged timeframes that are tunable through simple alteration of the hydrogel formulation. We demonstrate a relationship between hydrogel physical properties and the resulting immune response to immunization, whereby stiffer hydrogel formulations exhibit slower release and result in the greatest improvements to antibody responses while also enabling significant adjuvant dose sparing. In summary, this presentation will discuss the fundamental design characteristics, structural and materials characterization, and effective in vivo drug delivery application of a unique supramolecular hydrogel platform.

Injectable hydrogel property modulation for slow co-delivery of influenza subunit vaccine components enhances humoral immunity

ACS Spring 2022

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