Mucosal vaccination in mice provides protection from diverse respiratory threats.

Zhang, Haibo; Floyd, Katharine; Fang, Zhuoqing; Hoffmann, Filipe Araujo; Lee, Audrey; Froggatt, Heather Marie; Bharj, Gurpreet; Xie, Xia et al. · Science · 2026

basic_science · Level V

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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 a model antigen, ovalbumin, that provided broad, durable protection in mice for at least 3 months against infection with SARS-CoV-2 and <i>Staphylococcus aureus</i>. In addition, the vaccine protected mice from other viruses (SARS-CoV-2, SARS, SCH014 coronavirus), bacteria (<i>Acinetobacter baumannii</i>), and allergens. Protection was mediated by persistent ovalbumin-specific CD4<sup>+</sup> and CD8<sup>+</sup> memory T cells that imprinted alveolar macrophages (AMs), enhancing antigen presentation and antiviral immunity. 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.