A TLR7-nanoparticle adjuvant promotes broad immune responses against heterologous strains of Influenza and SARS-CoV-2

Abstract

Effective vaccines against viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple variant virus strains. However, antibody responses to current vaccines often lack cross-reactivity due to immunodominance. Here, we describe a polymeric toll-like receptor 7 agonist -nanoparticle adjuvant, TLR7-NP, 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 elicited cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T cell responses in mice. TLR7-NP adjuvanted influenza subunit vaccine successfully protects mice from heterologous viral challenge. TLR7-NP also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and mobilizes antiviral responses. Moreover, TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve the immune response to viral antigens, with promising implications for vaccine development.