The persistent threat of emerging coronaviruses highlights the critical need to establish frontline defenses directly at the respiratory entry portal. While intranasal immunization holds the promise of blocking infections at the respiratory portal of entry, the viscoelastic mucus barrier severely impedes the penetration of traditional vaccines, posing a significant challenge to the development of broad-spectrum mucosal immunity.
To overcome this, researchers developed a novel "mosaic" nanoparticle vaccine platform that successfully penetrates the mucus barrier to deliver broad-spectrum mucosal protection. By strategically selecting antigens based on viral serotype classifications and co-displaying them on gold nanoparticles, the team created a vaccine that induces broad neutralizing effects against a diverse array of coronaviruses, including highly evasive SARS-like and MERS-like strains.
"By rationally selecting antigens across different serotypes and co-displaying them on 5-nanometer carriers, this mosaic approach breaks through respiratory physiological barriers to establish robust frontline defenses," said Zezhong Liu, professor at the School of Pharmacy, Fudan University. "This provides a highly versatile strategy for next-generation broad-spectrum mucosal vaccines."
The success of this platform relies on the precise engineering of 5-nanometer gold nanocarriers, which are optimally sized for respiratory penetration. When administered intranasally with a STING agonist, these carriers efficiently navigate the mucus layer to enhance antigen uptake. This delivery mechanism effectively triggers profound mucosal immunity, characterized by the induction of high levels of local secretory IgA and the robust activation of lung tissue-resident memory T (TRM) cells, establishing durable deep-tissue immune memory.
This innovative vaccine chassis holds significant promise for rapid clinical translation, offering a proactive defense mechanism against continuous viral mutations. Moving forward, the research team aims to adapt this mosaic nanocarrier system to target other emerging and highly pathogenic respiratory viruses, paving the way for next-generation vaccines ready to combat future pandemic threats.
This work was conducted by researchers at the School of Pharmacy, Fudan University. The study, co-first authored by a graduate researcher specializing in advanced vaccine engineering, received critical support and funding from a national science and technology major project (grant number 2025ZD01903900).
About Author:
Dr. Zezhong Liu is a professor and lead researcher at the School of Pharmacy, Fudan University, specializing in prevention and treatment strategies for emerging infectious diseases, with a focus on antiviral vaccines, adjuvants, and antibody drugs. Notably, his team developed the novel STING agonist adjuvant CF501, which elicits broad-spectrum neutralizing antibodies against various SARS-CoV-2 variants by enhancing immune responses to conserved epitopes. Until now, Dr. Liu has published over 40 SCI-indexed papers, filed more than 10 patents, and led multiple major national research initiatives, including the National Science and Technology Major Project.
DOI Link:
https://doi.org/10.1016/j.hlife.2026.07.002
