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

Nat Mater. 2023 Mar;22(3):380-390. doi: 10.1038/s41563-022-01464-2. Epub 2023 Jan 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • COVID-19* / prevention & control
  • Humans
  • Immunity
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Mice
  • Nanoparticles*
  • SARS-CoV-2 / genetics
  • Toll-Like Receptor 7 / genetics
  • Vaccines, Subunit

Substances

  • Toll-Like Receptor 7
  • Influenza Vaccines
  • Adjuvants, Immunologic
  • Vaccines, Subunit
  • TLR7 protein, human