Virus-like structures for combination antigen protein mRNA vaccination

Nat Nanotechnol. 2024 Aug;19(8):1224-1233. doi: 10.1038/s41565-024-01679-1. Epub 2024 May 27.

Abstract

Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • Cell Adhesion Molecules / immunology
  • Dendritic Cells* / immunology
  • Female
  • Humans
  • Lectins, C-Type / immunology
  • Liposomes
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C*
  • Nanoparticles / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology
  • Vaccination / methods
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology
  • mRNA Vaccines / administration & dosage

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • COVID-19 Vaccines
  • RNA, Messenger
  • mRNA Vaccines
  • Angiotensin-Converting Enzyme 2
  • Lipid Nanoparticles
  • Lectins, C-Type
  • Receptors, Cell Surface
  • DC-specific ICAM-3 grabbing nonintegrin
  • ACE2 protein, human
  • Cell Adhesion Molecules
  • Vaccines, Virus-Like Particle
  • Liposomes

Supplementary concepts

  • SARS-CoV-2 variants