@article{5fb3764af2ec4eafb4f21eb40bdbe9f7,
title = "A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2",
abstract = "The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.",
author = "Qian Yin and Wei Luo and Vamsee Mallajosyula and Yang Bo and Jing Guo and Jinghang Xie and Meng Sun and Rohit Verma and Chunfeng Li and Constantz, \{Christian M.\} and Wagar, \{Lisa E.\} and Jing Li and Elsa Sola and Neha Gupta and Chunlin Wang and Oliver Kask and Xin Chen and Xue Yuan and Wu, \{Nicholas C.\} and Jianghong Rao and Chien, \{Yueh hsiu\} and Jianjun Cheng and Bali Pulendran and Davis, \{Mark M.\}",
note = "We thank X. Ji and M. Miranda for single-cell RNA-seq help, and the Stanford Nano Shared Facilities (SNSF), the Stanford Shared FACS Facility and the Human Immune Monitoring Centre at Stanford for assistance with this study, and members of the Davis laboratory for helpful advice and discussions. We thank N. King{\textquoteright}s group at the University of Washington for providing the SARS-CoV-2 antigen RBD-NP. We thank C. Yao for helping with schematic illustration. We are grateful for the support of the Howard Hughes Medical Institute and NIAID AI057229 (to M.M.D.), and the Bill and Melinda Gates Foundation INV003875 Discovery Hubs and Networks and OPP1113682 Centre for Human Systems Immunology (M.M.D.). We acknowledge the National Institutes of Health (grants R37 DK057665, R37 AI048638, U19 AI090023 and U19 AI057266), the Bill and Melinda Gates Foundation, the Soffer Fund endowment and Open Philanthropy to B.P. for supporting this work in B.P.{\textquoteright}s laboratory. We thank X. Ji and M. Miranda for single-cell RNA-seq help, and the Stanford Nano Shared Facilities (SNSF), the Stanford Shared FACS Facility and the Human Immune Monitoring Centre at Stanford for assistance with this study, and members of the Davis laboratory for helpful advice and discussions. We thank N. King{\textquoteright}s group at the University of Washington for providing the SARS-CoV-2 antigen RBD-NP. We thank C. Yao for helping with schematic illustration. We are grateful for the support of the Howard Hughes Medical Institute and NIAID AI057229 (to M.M.D.), and the Bill and Melinda Gates Foundation INV003875 Discovery Hubs and Networks and OPP1113682 Centre for Human Systems Immunology (M.M.D.). We acknowledge the National Institutes of Health (grants R37 DK057665, R37 AI048638, U19 AI090023 and U19 AI057266), the Bill and Melinda Gates Foundation, the Soffer Fund endowment and Open Philanthropy to B.P. for supporting this work in B.P.{\textquoteright}s laboratory.",
year = "2023",
month = mar,
doi = "10.1038/s41563-022-01464-2",
language = "English (US)",
volume = "22",
pages = "380--390",
journal = "Nature Materials",
issn = "1476-1122",
publisher = "Nature Publishing Group",
number = "3",
}