1. A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
- Author
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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, and Davis, Mark M
- Subjects
Lung ,Infectious Diseases ,Emerging Infectious Diseases ,Pneumonia ,Vaccine Related ,Biotechnology ,Bioengineering ,Immunization ,Pneumonia & Influenza ,Prevention ,Biodefense ,Influenza ,Nanotechnology ,3.4 Vaccines ,Prevention of disease and conditions ,and promotion of well-being ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Animals ,Mice ,Humans ,Influenza ,Human ,Toll-Like Receptor 7 ,SARS-CoV-2 ,COVID-19 ,Influenza Vaccines ,Adjuvants ,Immunologic ,Immunity ,Nanoparticles ,Vaccines ,Subunit ,Nanoscience & Nanotechnology - 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.
- Published
- 2023