Please use this identifier to cite or link to this item: http://repositorio.ufla.br/jspui/handle/1/43177
metadata.artigo.dc.title: Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes
metadata.artigo.dc.creator: Galili, Uri
metadata.artigo.dc.subject: COVID-19 - Vaccine
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
S-protein
Glycan shield
Anti-GAL Antibody
α-gal epitopes
metadata.artigo.dc.publisher: Elsevier
metadata.artigo.dc.date.issued: Sep-2020
metadata.artigo.dc.identifier.citation: GALILI, U. Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. Vaccine, [S.l.], v. 38, n. 42, p. 6487-6499, Sept. 2020.
metadata.artigo.dc.description.abstract: 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 α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) enables harnessing of the natural anti-Gal antibody for amplifying vaccine efficacy, as evaluated in mice producing anti-Gal. The α-gal epitope is the ligand for the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. Upon administration of vaccines presenting α-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 α-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 α-gal epitopes, will have similar amplifying effects on vaccine efficacy. α-Gal epitope synthesis on coronavirus vaccines can be achieved with recombinant α1,3galactosyltransferase, replication of the virus in cells with high α1,3galactosyltransferase activity as a result of stable transfection of cells with several copies of the α1,3galactosyltransferase gene (GGTA1), or by transduction of host cells with replication defective adenovirus containing this gene. In addition, recombinant S-protein presenting multiple α-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 α-gal epitopes may provide better protection than vaccines lacking this epitope because of increased uptake by APC.
metadata.artigo.dc.identifier.uri: https://www.sciencedirect.com/science/article/pii/S0264410X20310732
http://repositorio.ufla.br/jspui/handle/1/43177
metadata.artigo.dc.language: en_US
Appears in Collections:FCS - Artigos sobre Coronavirus Disease 2019 (COVID-19)

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