Mucosal vaccination in mice provides protection from diverse respiratory threats

Haibo Zhang(Stanford University), Katharine Floyd(Children's Healthcare of Atlanta), Zhuoqing Fang(Stanford University), Filipe Araujo Hoffmann(Stanford University), Audrey Lee(Stanford University), Heather Marie Froggatt(University of North Carolina at Chapel Hill), Gurpreet Bharj(Stanford University), Xia Xie(Stanford University), Haleigh B. Eppler(Stanford University), Jordan Mariah Santagata(Stanford University), Yanli Wang(Stanford University), M. J. C. Hu(Stanford University), Christopher B. Fox(University of Washington), Prabhu S. Arunachalam(University of Arizona), Ralph Baric(University of North Carolina at Chapel Hill), Mehul S. Suthar(Children's Healthcare of Atlanta), Bali Pulendran(Stanford University)
Science
February 19, 2026
10.1126/science.aea1260
Cited by 6

Abstract

Traditional vaccines target specific pathogens, limiting their scope against diverse respiratory threats. We describe an intranasal liposomal formulation combining toll-like receptor 4 and 7/8 ligands with a model antigen, ovalbumin, which provided broad, durable protection in mice for at least 3 months against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Staphylococcus aureus . In addition, the vaccine protected mice from other viruses (SARS-CoV-2, SARS, SHC014 coronavirus), bacteria ( Acinetobacter baumannii ), and allergens. Protection was mediated by persistent ovalbumin-specific CD4 + and CD8 + 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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