Journal Article

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

Kort, Thomas, Nathan, Margret, Wang, Lei, Liu, Ye V., Smith, Gale, Barnard, Dale L., Massare, Michael J.

2011

Overview

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 0.8μg 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 4μg 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.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adjuvants, Immunologic - administration & dosage / Allergy and Immunology / Aluminum / aluminum hydroxide / Aluminum Hydroxide - administration & dosage / Animals / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Applied microbiology / Baculoviridae - genetics / Baculovirus / Biological and medical sciences / Body Weight / chimerism / death / Disease Models, Animal / Female / Fundamental and applied biological sciences. Psychology / Genetic Vectors / glycoproteins / immune response / Immunogenicity / Influenza / Insecta / insects / Lung - virology / Lung virus titer / Medical research / Membrane Glycoproteins - genetics / Membrane Glycoproteins - immunology / Membrane Glycoproteins - metabolism / Mice / Mice, Inbred BALB C / Microbiology / Miscellaneous / Mortality / neutralizing antibodies / Neutralizing antibody / pandemic / Pandemics / people / Protein Multimerization / Public health / Recombinant Proteins - genetics / Recombinant Proteins - immunology / Recombinant Proteins - metabolism / Rodent Diseases - prevention & control / SARS coronavirus / Severe acute respiratory syndrome / Severe Acute Respiratory Syndrome - prevention & control / Severe acute respiratory syndrome coronavirus / Severe acute respiratory syndrome-related coronavirus - genetics / Severe acute respiratory syndrome-related coronavirus - immunology / Spike Glycoprotein, Coronavirus / Survival Analysis / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / 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 / Virology / Virus like particles / virus-like particle vaccines / weight loss