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Mucosal vaccination transcends pathogen boundaries to protect from diverse respiratory threats

ABSTRACT: Traditional vaccines target specific pathogens, limiting their scope against diverse respiratory threats. We describe an intranasal liposomal formulation combining Toll-like receptor (TLR) 4 and 7/8 ligands with ovalbumin that provides broad, durable protection for nearly seven months against such threats. In mice, it protected against viruses (SARS-CoV-2, influenza, SARS, SCH014 coronavirus), bacteria (Staphylococcus aureus, Streptococcus pneumoniae), and allergen. Protection was mediated by persistent ovalbumin-specific CD4⁺ and CD8⁺ lung memory T cells that imprinted alveolar macrophages (AMs) via RANKL, enhancing antigen presentation and antiviral immunity; depletion of AMs, abolished protection, while their transfer restored it. Following infection, vaccinated mice mounted rapid pathogen-specific T-cell and antibody responses and formed ectopic lymphoid structures in the lung. These results reveal a class of “universal vaccines,” against diverse respiratory threats.

ORGANISM(S): Mus musculus

PROVIDER: GSE310116 | GEO | 2026/02/23

REPOSITORIES: GEO

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