title: 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.affiliation: Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States. yliu@novavax.com
authors.forename: Ye V
authors.initials: YV
authors.lastname: Liu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Massare
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
authors.forename: Thomas
authors.initials: T
authors.lastname: Kort
authors.forename: Margret
authors.initials: M
authors.lastname: Nathan
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Gale
authors.initials: G
authors.lastname: Smith
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae / Q000235:genetics; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D007313:Insecta; D008168:Lung / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012376:Rodent Diseases / Q000517:prevention & control; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D016019:Survival Analysis; D022721:Vaccines, Virosome / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C488936:M1 protein, Influenza A virus; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D022721:Vaccines, Virosome; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D000536:Aluminum Hydroxide