The characterization of technical design of a virus-like structure (VLS) nanodelivery system as vaccine candidate against SARS-CoV-2 variants

Hum Vaccin Immunother. 2025 Dec;21(1):2473183. doi: 10.1080/21645515.2025.2473183. Epub 2025 Mar 5.

Abstract

The constant mutation of SARS-CoV-2 has led to the continuous appearance of viral variants and their pandemics and has improved the development of vaccines with a broad spectrum of antigens to curb the spread of the virus. The work described here suggested a novel vaccine with a virus-like structure (VLS) composed of combined mRNA and protein that is capable of stimulating the immune system in a manner similar to that of viral infection. This VLS vaccine is characterized by its ability to specifically target dendritic cells and/or macrophages through S1 protein recognition of the DC-SIGN receptor in cells, which leads to direct mRNA delivery to these innate immune cells for activation of robust immunity with a broad spectrum of neutralizing antibodies and immune protective capacity against variants. Research on its composition characteristics and structural features has suggested its druggability. Compared with the current mRNA vaccine, the VLS vaccine was identified as having no cytotoxicity at its effective application dosage, while the results of safety observations in animals revealed fewer adverse reactions during immunization.

Keywords: Virus-like structure; dosage; immunity; mRNA vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Cell Adhesion Molecules
  • DC-Specific ICAM-3 Grabbing Nonintegrin
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Lectins, C-Type / immunology
  • Macrophages / immunology
  • Mice
  • Receptors, Cell Surface / immunology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccines, Virus-Like Particle* / administration & dosage
  • Vaccines, Virus-Like Particle* / immunology

Substances

  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, Virus-Like Particle
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Cell Adhesion Molecules
  • DC-Specific ICAM-3 Grabbing Nonintegrin
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants