Development and Evaluation of a Newcastle Disease Virus-like Particle Vaccine Expressing SARS-CoV-2 Spike Protein with Protease-Resistant and Stability-Enhanced Modifications

Viruses. 2024 Dec 18;16(12):1932. doi: 10.3390/v16121932.

Abstract

The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity. Using a prime-boost regimen, we administered NDV-VLP-S-3Q2P intramuscularly at different doses (2, 10, and 20 µg) to BALB/c mice. Robust humoral responses were observed, with high titers of S-protein-specific IgG and neutralizing antibodies against SARS-CoV-2 pseudovirus, reaching titers of 1:2200-1:2560 post-boost. The vaccine also induced balanced Th1/Th2 immune responses, evidenced by significant upregulation of cytokines (IFN-γ, IL-2, and IL-4) and S-protein-specific IgG1 and IgG2a. Furthermore, strong activation of CD4+ and CD8+ T cells in the spleen and lungs confirmed the vaccine's ability to promote cellular immunity. These findings demonstrate that NDV-S3Q2P-VLP is a potent immunogen capable of eliciting robust humoral and cellular immune responses, highlighting its potential as a promising candidate for further clinical development in combating COVID-19.

Keywords: NDV; SARS-CoV-2; VLP; immune response; vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C*
  • Newcastle disease virus* / genetics
  • Newcastle disease virus* / immunology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology
  • Vaccines, Virus-Like Particle* / administration & dosage
  • Vaccines, Virus-Like Particle* / genetics
  • Vaccines, Virus-Like Particle* / immunology

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Antibodies, Neutralizing
  • Vaccines, Virus-Like Particle
  • Immunoglobulin G