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Updated: Jun 19, 2026

A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Precision-engineered STING agonist nanoparticles enable coordinated mucosal-systemic immunity for durable
Zezhong Liu1, Jie Zhou2,3, Ruiyu Gao4
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Department of Pharmacology, the Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, School of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China. zezhongliu@fudan.edu.cn.
A novel nanoparticle adjuvant, NanoCF501, enables localized mucosal immunity with minimal systemic exposure. This STING agonist enhances vaccine efficacy and broad protection against respiratory viruses, advancing nanomedicine for pandemic preparedness.
Area of Science:
- Nanomedicine
- Vaccinology
- Immunology
Background:
- Developing mucosal vaccines faces challenges in achieving localized immunity without systemic toxicity.
- Targeting the respiratory tract for vaccination requires efficient mucus penetration and retention.
Purpose of the Study:
- To engineer NanoCF501, a nanoparticulate STING agonist, as an adjuvant for mucosal vaccine delivery.
- To evaluate NanoCF501's ability to induce localized immunity and systemic protection against respiratory viruses.
- To assess NanoCF501's potential for repurposing existing vaccines for mucosal administration.
Main Methods:
- NanoCF501 was formulated using a 2-ethyl-2-oxazoline polymer.
- Pharmacokinetic studies in rats assessed systemic exposure.
- Intranasal co-administration with viral antigens in mice and non-human primates.
- Single-cell transcriptomics analyzed lung antigen-presenting cell responses.
- Licensed influenza vaccines were repurposed for mucosal delivery.
Main Results:
- NanoCF501 demonstrated efficient mucus penetration and localized respiratory retention with minimal systemic exposure.
- Intranasal NanoCF501 induced robust mucosal and systemic immunity against pan-β-coronaviruses in mice.
- STING-dependent reprogramming of lung antigen-presenting cells was observed, enhancing adaptive immunity.
- NanoCF501 successfully repurposed licensed influenza vaccines for mucosal delivery in non-human primates.
Conclusions:
- NanoCF501 serves as a universal adjuvant for next-generation vaccines, enabling localized mucosal immunity.
- This nanomedicine approach advances pandemic preparedness by enhancing vaccine delivery and efficacy.
- NanoCF501 facilitates the repurposing of intramuscular antigens for effective mucosal vaccination.

