Intranasal gold nanoparticle-antigen induces mucosal and systemic immunity against β-coronaviruses.
Abstract
The continued emergence of diverse beta-coronaviruses (β-CoVs) from animal reservoirs underscores the urgent need for broad-spectrum mucosal vaccines, yet their development is hindered by physiological barriers, rapid antigen clearance, and suboptimal multivalent display strategies. To address this, we intranasally immunized BALB/c mice (n = 3 or 4 per group) with 5 or 15 nm gold nanoparticles (AuNPs) displaying the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD, 5 μg per mouse) and adjuvanted with the STING agonist cGAMP (20 μg per mouse). Guided by the serotyping of STING agonist-elicited neutralizing responses, we generated AuNP-Mix co-displaying six representative β-CoV RBDs for comparative immunological evaluation against single-RBD AuNP formulations. Antigen delivery, pulmonary retention, mucosal and systemic immune responses were evaluated via in vivo imaging, enzyme-linked immunosorbent assays, pseudovirus neutralization assays, flow cytometry, immunofluorescence, and challenge studies. We demonstrated that 5 nm AuNP-RBD adjuvanted with cGAMP exhibited superior mucosal penetration and lung retention, induced robust local and systemic immunity, and elicited cross-neutralizing antibodies against SARS-CoV-2 variants, SARS-CoV, and SARS-related coronaviruses. Intranasal immunization with AuNP-Mix elicited broader mucosal/systemic immune responses than those achieved with simple RBD mixtures, as demonstrated by its potent neutralizing activity against SARS-CoV-2 variants, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and divergent MERS-like viruses. These findings establish AuNP-based mosaic display as a versatile platform for next-generation mucosal vaccines.
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BibTeX
@article{wang2026intranasal,
title = {{Intranasal gold nanoparticle-antigen induces mucosal and systemic immunity against β-coronaviruses.}},
author = {Muzhuo Wang and Weijie Wang and Wei Xu and Zhikai Chen and Junlan Zhang and Zeya Li and Jiadong Li and Shibo Jiang and Lu Lu and Zezhong Liu},
journal = {HLife},
year = {2026},
month = jul,
doi = {10.1016/j.hlife.2026.07.002},
url = {https://europepmc.org/article/MED/42904043},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Intranasal gold nanoparticle-antigen induces mucosal and systemic immunity against β-coronaviruses.
AU - Muzhuo Wang
AU - Weijie Wang
AU - Wei Xu
AU - Zhikai Chen
AU - Junlan Zhang
AU - Zeya Li
AU - Jiadong Li
AU - Shibo Jiang
AU - Lu Lu
AU - Zezhong Liu
PY - 2026
DA - 2026/07/22
JO - HLife
DO - 10.1016/j.hlife.2026.07.002
UR - https://europepmc.org/article/MED/42904043
AB - The continued emergence of diverse beta-coronaviruses (β-CoVs) from animal reservoirs underscores the urgent need for broad-spectrum mucosal vaccines, yet their development is hindered by physiological barriers, rapid antigen clearance, and suboptimal multivalent display strategies. To address this, we intranasally immunized BALB/c mice (n = 3 or 4 per group) with 5 or 15 nm gold nanoparticles (AuNPs) displaying the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD, 5 μg per mouse) and adjuvanted with the STING agonist cGAMP (20 μg per mouse). Guided by the serotyping of STING agonist-elicited neutralizing responses, we generated AuNP-Mix co-displaying six representative β-CoV RBDs for comparative immunological evaluation against single-RBD AuNP formulations. Antigen delivery, pulmonary retention, mucosal and systemic immune responses were evaluated via in vivo imaging, enzyme-linked immunosorbent assays, pseudovirus neutralization assays, flow cytometry, immunofluorescence, and challenge studies. We demonstrated that 5 nm AuNP-RBD adjuvanted with cGAMP exhibited superior mucosal penetration and lung retention, induced robust local and systemic immunity, and elicited cross-neutralizing antibodies against SARS-CoV-2 variants, SARS-CoV, and SARS-related coronaviruses. Intranasal immunization with AuNP-Mix elicited broader mucosal/systemic immune responses than those achieved with simple RBD mixtures, as demonstrated by its potent neutralizing activity against SARS-CoV-2 variants, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and divergent MERS-like viruses. These findings establish AuNP-based mosaic display as a versatile platform for next-generation mucosal vaccines.
SN - 2949-9283
ER -