Yin, QianLuo, WeiMallajosyula, VamseeBo, YangGuo, JingXie, JinghangSun, MengVerma, RohitLi, ChunfengConstantz, Christian M.Wagar, Lisa E.Li, JingSola, ElsaGupta, NehaWang, ChunlinKask, OliverChen, XinYuan, XueWu, Nicholas C.Rao, JianghongChien, Yueh-hsiuCheng, JianjunPulendran, BaliDavis, Mark M.2023-11-202023-11-202023Yin Q, Luo W, Mallajosyula V, et al. A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2. Nat Mater. 2023;22(3):380-390. doi:10.1038/s41563-022-01464-2https://hdl.handle.net/1805/37167The 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.en-USAttribution 4.0 InternationalCOVID-19Influenza vaccinesNanoparticlesSARS-CoV-2Toll-like receptor 7Article