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.

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.

• Authors: Ye V Liu, Michael J Massare, Dale L Barnard, Thomas Kort, Margret Nathan, Lei Wang, Gale Smith
• Journal: Vaccine (Vaccine) Vol. 29 Issue 38 Pg. 6606-13 (Sep 02 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 21762752 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 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

Topics

• 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, immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Protein Multimerization
• Recombinant Proteins (genetics, immunology, metabolism)
• Rodent Diseases (prevention & control)
• Severe acute respiratory syndrome-related coronavirus (genetics, immunology)
• Severe Acute Respiratory Syndrome (prevention & control)
• Spike Glycoprotein, Coronavirus
• Survival Analysis
• Vaccines, Virosome (genetics, immunology)
• Viral Envelope Proteins (genetics, immunology, metabolism)
• Viral Load
• Viral Matrix Proteins (genetics, metabolism)
• Viral Vaccines (genetics, immunology)