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A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.
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; Davis, Mark M.
  • Yin Q; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Luo W; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Mallajosyula V; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Bo Y; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Guo J; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Xie J; Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Sun M; Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
  • Verma R; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Li C; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Constantz CM; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Wagar LE; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Li J; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Sola E; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Gupta N; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Wang C; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Kask O; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Chen X; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Yuan X; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Wu NC; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Rao J; Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Chien YH; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Cheng J; Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
  • Pulendran B; Department of Chemistry, Stanford University, Stanford, CA, USA.
  • Davis MM; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
Nat Mater ; 22(3): 380-390, 2023 03.
Article in English | MEDLINE | ID: covidwho-2221825
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Influenza, Human / Nanoparticles / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Mater Journal subject: Science / Chemistry Year: 2023 Document Type: Article Affiliation country: S41563-022-01464-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Influenza, Human / Nanoparticles / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Mater Journal subject: Science / Chemistry Year: 2023 Document Type: Article Affiliation country: S41563-022-01464-2