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Science . Mucosal vaccination in mice provides protection from diverse respiratory threats

tetano

Editor, Senior Moderator
Science


. 2026 Feb 19:eaea1260.
doi: 10.1126/science.aea1260. Online ahead of print.
Mucosal vaccination in mice provides protection from diverse respiratory threats

Haibo Zhang[SUP] 1 [/SUP], Katharine Floyd[SUP] 2 [/SUP], Zhuoqing Fang[SUP] 1 [/SUP], Filipe Araujo Hoffmann[SUP] 1 [/SUP], Audrey Lee[SUP] 1 [/SUP], Heather Marie Froggatt[SUP] 3 [/SUP], Gurpreet Bharj[SUP] 1 [/SUP], Xia Xie[SUP] 1 [/SUP], Haleigh B Eppler[SUP] 1 [/SUP], Jordan Mariah Santagata[SUP] 1 [/SUP], Yanli Wang[SUP] 1 [/SUP], Mengyun Hu[SUP] 1 [/SUP], Christopher B Fox[SUP] 4 5 [/SUP], Prabhu S Arunachalam[SUP] 6 [/SUP], Ralph Baric[SUP] 3 [/SUP], Mehul S Suthar[SUP] 2 [/SUP], Bali Pulendran[SUP] 1 7 8 [/SUP]


Affiliations
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 Staphylococcus aureus. In addition, the vaccine protected mice from other viruses (SARS-CoV-2, SARS, SCH014 coronavirus), bacteria (Acinetobacter baumannii), 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.


 
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