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Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes.
Vaccine. 2020 09 29; 38(42):6487-6499.V

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.

Authors+Show Affiliations

Department of Medicine, Rush Medical School, Chicago, IL, USA. Electronic address: Uri.Galili@rcn.com.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32907757

Citation

Galili, Uri. "Amplifying Immunogenicity of Prospective Covid-19 Vaccines By Glycoengineering the Coronavirus Glycan-shield to Present Α-gal Epitopes." Vaccine, vol. 38, no. 42, 2020, pp. 6487-6499.
Galili U. Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. Vaccine. 2020;38(42):6487-6499.
Galili, U. (2020). Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. Vaccine, 38(42), 6487-6499. https://doi.org/10.1016/j.vaccine.2020.08.032
Galili U. Amplifying Immunogenicity of Prospective Covid-19 Vaccines By Glycoengineering the Coronavirus Glycan-shield to Present Α-gal Epitopes. Vaccine. 2020 09 29;38(42):6487-6499. PubMed PMID: 32907757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. A1 - Galili,Uri, Y1 - 2020/08/19/ PY - 2020/05/08/received PY - 2020/07/22/revised PY - 2020/08/12/accepted PY - 2020/9/11/pubmed PY - 2020/10/3/medline PY - 2020/9/10/entrez KW - Covid-19 vaccine KW - Glycan shield KW - S-protein KW - SARS-CoV-2 KW - anti-Gal KW - α-gal epitopes SP - 6487 EP - 6499 JF - Vaccine JO - Vaccine VL - 38 IS - 42 N2 - 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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/32907757/Amplifying_immunogenicity_of_prospective_Covid_19_vaccines_by_glycoengineering_the_coronavirus_glycan_shield_to_present_α_gal_epitopes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(20)31073-2 DB - PRIME DP - Unbound Medicine ER -