Precision-engineered STING agonist nanoparticles enable coordinated mucosal-systemic immunity for durable pan-β-coronavirus protection.

Summary

Preclinical engineering of a STING-agonist nanoparticle adjuvant (NanoCF501) achieved strong mucosal and systemic immunity with localized respiratory retention and minimal systemic exposure. It protected against homologous and heterologous β-coronaviruses in mice, validated in non-human primates, and repurposed licensed influenza antigens for intranasal delivery.

Key Findings

• NanoCF501 showed efficient mucus penetration and localized respiratory retention with minimal systemic exposure in rats.
• Intranasal NanoCF501 plus multivalent coronavirus antigen induced robust mucosal (e.g., IgA) and systemic immunity, protecting against homologous and heterologous β-coronaviruses in mice.
• Single-cell transcriptomics revealed STING-dependent reprogramming of lung antigen-presenting cells, enhancing adaptive responses.
• Efficacy signals were validated in non-human primates and extended to repurpose licensed influenza vaccines for mucosal delivery.

Clinical Implications

While preclinical, the platform could enable intranasal boosting and broader, durable protection with reduced systemic reactogenicity, informing next-generation respiratory vaccine strategies and rapid pandemic responses.

Limitations

• Preclinical stage; human safety, dose, and efficacy remain to be demonstrated
• Durability and breadth across divergent sarbecoviruses/merbecoviruses in humans are unknown

Future Directions

Early-phase clinical trials to evaluate safety, dosing, and mucosal immunogenicity; comparative studies against current adjuvants; and testing as heterologous boosters for existing intramuscular vaccines.