Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine*

Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9467-9473. doi: 10.1002/anie.202015362. Epub 2021 Mar 11.

Abstract

The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile. It is water-soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ-PEG-CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS-CoV-2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.

Keywords: COVID-19; SARS-CoV-2; amphiphiles; innate immunity; vaccines.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / immunology
  • COVID-19 Vaccines / therapeutic use*
  • Cholesterol / analogs & derivatives
  • Cholesterol / immunology
  • Cholesterol / therapeutic use
  • Female
  • Humans
  • Imidazoles / immunology
  • Imidazoles / therapeutic use*
  • Immunity, Innate / drug effects*
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza Vaccines / immunology
  • Influenza Vaccines / therapeutic use
  • Influenza, Human / prevention & control
  • Membrane Glycoproteins / agonists
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Polyethylene Glycols / therapeutic use
  • Quinolines / immunology
  • Quinolines / therapeutic use*
  • Recombinant Proteins / immunology
  • SARS-CoV-2 / drug effects
  • Spike Glycoprotein, Coronavirus / immunology
  • Surface-Active Agents / therapeutic use
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 8 / agonists

Substances

  • Adjuvants, Immunologic
  • COVID-19 Vaccines
  • Imidazoles
  • Influenza Vaccines
  • Membrane Glycoproteins
  • Quinolines
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Surface-Active Agents
  • TLR8 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • spike protein, SARS-CoV-2
  • Polyethylene Glycols
  • Cholesterol