Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

Vaccine. 2011 Sep 2;29(38):6606-13. doi: 10.1016/j.vaccine.2011.06.111. Epub 2011 Jul 14.

Abstract

SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Aluminum Hydroxide / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Baculoviridae / genetics
  • Body Weight
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Insecta
  • Lung / virology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Multimerization
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Rodent Diseases / prevention & control
  • SARS Virus / genetics
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Spike Glycoprotein, Coronavirus
  • Survival Analysis
  • Vaccines, Virosome / genetics
  • Vaccines, Virosome / immunology
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism
  • Viral Load
  • Viral Matrix Proteins / genetics*
  • Viral Matrix Proteins / metabolism
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • M1 protein, Influenza A virus
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Virosome
  • Viral Envelope Proteins
  • Viral Matrix Proteins
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus
  • Aluminum Hydroxide