A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

• Published in: Nature materials 2023-03, Vol.22 (3), p.380-390
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; 631/250/590/2291; 639/925/352/152; adjuvants; Adjuvants, Immunologic - pharmacology; Animals; Antibodies; Antigens; Biomaterials; Chemistry and Materials Science; Condensed Matter Physics; COVID-19; COVID-19 - prevention & control; drug delivery; Humans; Immune response; Immune system; Immunity; Influenza; Influenza Vaccines; Influenza, Human - prevention & control; Materials Science; Mice; Nanoparticles; Nanotechnology; Optical and Electronic Materials; Robustness; SARS-CoV-2 - genetics; Severe acute respiratory syndrome coronavirus 2; Toll-Like Receptor 7 - genetics; Vaccines; Vaccines, Subunit; Viral diseases
• ISSN: 1476-1122; 1476-4660; 1476-4660
• DOI: 10.1038/s41563-022-01464-2

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. A nanoparticle-based adjuvant incorporating a Toll-like receptor 7 agonist elicits cross-reactive antibodies for both dominant and subdominant epitopes and enhances immune responses against multiple variants of influenza and SARS-CoV-2.