A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice

Abstract

A recombinant SARS-CoV spike (S) glycoprotein vaccine produced in insect cells in a pre-clinical development stage is described. A truncated version of S glycoprotein, containing only the ecto-domain, as well as a His-tagged full-length version were cloned and expressed in a serum-free insect cell line, ExpresSF+. The proteins, purified to apparent homogeneity by liquid column chromatography, were formulated without adjuvant at 3, 9, 27, and 50 microg per dose in phosphate saline and used to immunize mice. Both antigens in each formulation elicited a strong immune response after two or three vaccinations with the antigen. Neutralizing antibody titers correlated closely with standard ELISA reactivity against the S glycoprotein. The truncated S protein was also formulated with an adjuvant, aluminum hydroxide, at 1 microg per dose (+/-adjuvant), and 5 microg per dose (+/-adjuvant). Significantly enhanced immune responses, manifested by higher titers of serum ELISA and viral neutralizing antibodies, were achieved in adjuvanted groups with fewer doses and lower concentration of S glycoprotein. These findings indicate that the ecto-domain of SARS-CoV S glycoprotein vaccine, with or without adjuvant, is immunogenic and induces high titers of virus neutralizing antibodies to levels similar to those achieved with the full S glycoprotein vaccine.

Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies

“…The emergence of the SARS-CoV has also led to the development of new vaccine strategies, including expression of SARS-CoV spike protein in other viruses [77,78,79,80,81,82,83,84,85], inactivated SARS-CoV particles [82,86,87,88,89,90,91] or DNA vaccines [92,93,94,95]. However, an early concern for application of a SARS-CoV vaccine was the experience with animal coronavirus vaccines, which induced enhanced disease and immunopathology in animals when challenged with infectious virus [96].…”

Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection

“…Several vaccine strategies proposed for prevention of SARS include inactivated virus-based vaccines (15), DNA-based vaccines (16), recombinant subunit vaccines (17), and viral vector-based vaccines (18). These vaccine candidates are able to induce protective immune responses against SARS-CoV, including NA and T cell immune responses (14, 19 -21).…”

“…They can effectively induce NA, cellular, and/or protective immune responses against SARS-CoV (16,17,22). However, some may cause liver damage in those vaccinated animals, in which SARS-CoV infection was not prevented by the mobilized immune responses (27,28).…”

Recombinant protein subunit vaccine synthesis in microbes: a role for yeast?

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