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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)380-390
Number of pages11
JournalNature Materials
Volume22
Issue number3
DOIs
StatePublished - Mar 2023

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering
  • General Chemistry
  • General Materials Science

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