Title : Modular protein nanorings for next-generation immunoengineering

Immune interventions remain constrained by limited nanoscale control over how antigens and immune signals are presented, creating an immunoengineering bottleneck that impacts both communicable diseases (e.g., rapidly evolving influenza) and non-communicable diseases (e.g., Parkinson’s disease). Here we present a protein-based nanotechnology platform of modular nanorings—Multicomponent Ring-Like Particles (RLPs)—designed as programmable immune interfaces with tunable epitope identity, conformation, spatial organization, and innate activation. RLPs form by rapid bottom-up self-assembly of a ring-like protein scaffold (~40 nm diameter; 24 protomers) and an on-demand library of interchangeable functional modules, including antigens/epitopes, innate agonists (e.g., flagellin/TLR5), and targeting interfaces (e.g., Z-domain, SpyCatcher, monomeric streptavidin). This modular architecture enables precise control of multivalency and co-display at the single-nanoparticle level without chemical conjugation, thereby avoiding reaction by-products and supporting a simple, cost-effective, cargo-agnostic manufacturing workflow. We have validated >30 cargoes spanning 1–120 kDa, with up to four components codisplayed per particle. Beyond structural programmability, RLPs exhibit functional nano-bio performance: they enhance antigen uptake and selectively activate dendritic cells in vitro. In preclinical mouse studies, formulations administered intramuscularly, subcutaneously, intraperitoneally, or intranasally were well tolerated and elicited high antibody titers with tunable innate activation, with no detectable adverse effects. Two near-term use cases illustrate the platform’s breadth: rapidly updatable multivalent influenza nanovaccines to reduce strain mismatch and support pandemic preparedness, and a Parkinson’s immunotherapy that elicits antibodies selective for toxic α-synuclein conformers while sparing monomer. Overall, modular nanorings provide a scalable, reconfigurable nanotechnology platform for vaccines, immunotherapies, and diagnostic immunoreagents.

Salvador Ventura is Professor of Biochemistry and Molecular Biology at the Autonomous University of Barcelona (UAB) and co-founder of Eureka Nanobioengineering. He has received prestigious awards, including the Bruker 'Manuel Rico' Prize, four ICREA Academia awards, the Narcís Monturiol Med al, and the Serra Hunter Knowledge Transference Award. Salvador is a member of the Academia Europaea. As a Group Leader at the Institute of Biotechnology and Biomedicine (IBB) of UAB, where he previously served as Director, he has authored over 320 scientific publications and holds 19 patents.