Mucosal vaccination in mice provides protection from diverse respiratory threats
- Haibo Zhang
- Katharine Floyd
- Zhuoqing Fang
- Filipe Araujo Hoffmann
- Audrey Lee
- Heather Marie Froggatt
- Gurpreet Bharj
- Xia Xie
- Haleigh B. Eppler
- Jordan Mariah Santagata
- Yanli Wang
- Mengyun Hu
- Christopher B. Fox
- Prabhu S. Arunachalam
- Ralph Baric
- Mehul S. Suthar
- Bali Pulendran
2026-02-19
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 + 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.