- Yin, Qian;
- Luo, Wei;
- Mallajosyula, Vamsee;
- Bo, Yang;
- Guo, Jing;
- Xie, Jinghang;
- Sun, Meng;
- Verma, Rohit;
- Li, Chunfeng;
- Constantz, Christian M;
- Wagar, Lisa E;
- Li, Jing;
- Sola, Elsa;
- Gupta, Neha;
- Wang, Chunlin;
- Kask, Oliver;
- Chen, Xin;
- Yuan, Xue;
- Wu, Nicholas C;
- Rao, Jianghong;
- Chien, Yueh-hsiu;
- Cheng, Jianjun;
- Pulendran, Bali;
- Davis, Mark M
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.