Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes

The many carbohydrate chains on Covid-19 coronavirus SARS-CoV-2 and its S-protein form a glycan-shield that masks antigenic peptides and decreases uptake of inactivated virus or S-protein vaccines by APC. Studies on inactivated influenza virus and recombinant gp120 of HIV vaccines indicate that glycoengineering of glycan-shields to present alpha-gal epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) enables harnessing of the natural anti-Gal antibody for amplifying vaccine efficacy, as evaluated in mice producing anti-Gal. The alpha-gal epitope is the ligand for the natural anti-Gal antibody which constitutes similar to 1% of immunoglobulins in humans. Upon administration of vaccines presenting alpha-gal epitopes, anti-Gal binds to these epitopes at the vaccination site and forms immune complexes with the vaccines. These immune complexes are targeted for extensive uptake by APC as a result of binding of the Fc portion of immunocomplexed anti-Gal to Fc receptors on APC. This anti-Gal mediated effective uptake of vaccines by APC results in 10-200-fold higher anti-viral immune response and in 8-fold higher survival rate following challenge with a lethal dose of live influenza virus, than same vaccines lacking alpha-gal epitopes. It is suggested that glycoengineering of carbohydrate chains on the glycan-shield of inactivated SARS-CoV-2 or on S-protein vaccines, for presenting alpha-gal epitopes, will have similar amplifying effects on vaccine efficacy. alpha-Gal epitope synthesis on coronavirus vaccines can be achieved with recombinant alpha 1,3galactosyltransferase, replication of the virus in cells with high alpha 1,3galactosyltransferase activity as a result of stable transfection of cells with several copies of the alpha 1,3galactosyltransferase gene (GGTA1), or by transduction of host cells with replication defective adenovirus containing this gene. In addition, recombinant S-protein presenting multiple alpha-gal epitopes on the glycan-shield may be produced in glycoengineered yeast or bacteria expression systems containing the corresponding glycosyltransferases. Prospective Covid-19 vaccines presenting alpha-gal epitopes may provide better protection than vaccines lacking this epitope because of increased uptake by APC. (C) 2020 The Author. Published by Elsevier Ltd.