tetano
Editor, Senior Moderator
Nat Mater
. 2023 Jan 30.
doi: 10.1038/s41563-022-01464-2. Online ahead of print.
A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
Qian Yin[SUP] #[/SUP][SUP] 1 [/SUP], Wei Luo[SUP] #[/SUP][SUP] 1 2 [/SUP], Vamsee Mallajosyula[SUP] 1 [/SUP], Yang Bo[SUP] 3 [/SUP], Jing Guo[SUP] 4 [/SUP], Jinghang Xie[SUP] 5 [/SUP], Meng Sun[SUP] 1 [/SUP], Rohit Verma[SUP] 1 [/SUP], Chunfeng Li[SUP] 1 [/SUP], Christian M Constantz[SUP] 1 [/SUP], Lisa E Wagar[SUP] 1 6 [/SUP], Jing Li[SUP] 1 [/SUP], Elsa Sola[SUP] 1 [/SUP], Neha Gupta[SUP] 1 [/SUP], Chunlin Wang[SUP] 1 [/SUP], Oliver Kask[SUP] 1 [/SUP], Xin Chen[SUP] 1 [/SUP], Xue Yuan[SUP] 7 [/SUP], Nicholas C Wu[SUP] 8 [/SUP], Jianghong Rao[SUP] 5 9 [/SUP], Yueh-Hsiu Chien[SUP] 1 4 [/SUP], Jianjun Cheng[SUP] 3 [/SUP], Bali Pulendran[SUP] 10 11 12 [/SUP], Mark M Davis[SUP] 13 14 15 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
. 2023 Jan 30.
doi: 10.1038/s41563-022-01464-2. Online ahead of print.
A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
Qian Yin[SUP] #[/SUP][SUP] 1 [/SUP], Wei Luo[SUP] #[/SUP][SUP] 1 2 [/SUP], Vamsee Mallajosyula[SUP] 1 [/SUP], Yang Bo[SUP] 3 [/SUP], Jing Guo[SUP] 4 [/SUP], Jinghang Xie[SUP] 5 [/SUP], Meng Sun[SUP] 1 [/SUP], Rohit Verma[SUP] 1 [/SUP], Chunfeng Li[SUP] 1 [/SUP], Christian M Constantz[SUP] 1 [/SUP], Lisa E Wagar[SUP] 1 6 [/SUP], Jing Li[SUP] 1 [/SUP], Elsa Sola[SUP] 1 [/SUP], Neha Gupta[SUP] 1 [/SUP], Chunlin Wang[SUP] 1 [/SUP], Oliver Kask[SUP] 1 [/SUP], Xin Chen[SUP] 1 [/SUP], Xue Yuan[SUP] 7 [/SUP], Nicholas C Wu[SUP] 8 [/SUP], Jianghong Rao[SUP] 5 9 [/SUP], Yueh-Hsiu Chien[SUP] 1 4 [/SUP], Jianjun Cheng[SUP] 3 [/SUP], Bali Pulendran[SUP] 10 11 12 [/SUP], Mark M Davis[SUP] 13 14 15 [/SUP]
Affiliations
- PMID: 36717665
- DOI: 10.1038/s41563-022-01464-2
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[SUP]+[/SUP] 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.