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, M. J. C. Hu, Christopher B. Fox, Prabhu S. Arunachalam, Ralph Baric, Mehul S. Suthar, Bali Pulendran
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.