A biomimetic multi-component subunit vaccine via ratiometric loading of hierarchical hydrogels

Fanfan Du, Simseok A. Yuk, Yuan Qian, El Hadji Arona Mbaye, Michael P. Vincent, Sharan Bobbala, Tirzah M. Abbott, Hyeohn Kim, Yang Li, Haoyu Li, Sijia Yi, Baofu Qiao and Evan A. Scott ()
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Fanfan Du: University of Virginia School of Medicine
Simseok A. Yuk: Northwestern University
Yuan Qian: Northwestern University
El Hadji Arona Mbaye: Northwestern University
Michael P. Vincent: Northwestern University
Sharan Bobbala: Northwestern University
Tirzah M. Abbott: Northwestern University Atomic and Nanoscale Characterization Experimental Center
Hyeohn Kim: Northwestern University
Yang Li: Northwestern University
Haoyu Li: Northwestern University
Sijia Yi: Northwestern University
Baofu Qiao: City University of New York
Evan A. Scott: University of Virginia School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract The development of subunit vaccines that mimic the molecular complexity of attenuated vaccines has been limited by the difficulty of intracellular co-delivery of multiple chemically diverse payloads at controllable concentrations. We report on hierarchical hydrogel depots employing simple poly(propylene sulfone) homopolymers to enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants in a hierarchical manner. The optimized vaccine consisted of immunostimulants either adsorbed to or encapsulated within nanogels, which were capable of noncovalent anchoring to subcutaneous tissues. In female BALB/c and C57BL/6 mice, these 5-component nanogel vaccines demonstrated enhanced humoral and cell-mediated immune responses compared to formulations with standard single adjuvant and antigen pairing. The use of a single simple homopolymer capable of rapid and stable loading and intracellular delivery of diverse molecular cargoes holds promise for facile development and optimization of scalable subunit vaccines and complex therapeutic formulations for a wide range of biomedical applications.

Date: 2025
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DOI: 10.1038/s41467-025-60416-x

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