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首页> 外文期刊>Vaccine >Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present alpha-gal epitopes
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Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present alpha-gal epitopes

机译：通过Glycoengering The Coronavirus Glycan-Shield扩增预期Covid-19疫苗的免疫原性，以呈现α-Gal表层

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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.
机译：Covid-19冠状病毒SARS-COV-2上的许多碳水化合物链和其S蛋白形成糖粉屏蔽，其掩盖抗原肽并通过APC降低灭活病毒或S蛋白疫苗的摄取。关于艾滋病毒疫苗的灭活流感病毒和重组GP120的研究表明，甘油屏蔽的甘油池含有α-加仑表位（Galα1-3Galβ1-4GlCNAC-R）能够利用用于扩增疫苗疗效的天然抗GAL抗体，如在生产抗GAL的小鼠中评价。 α-GAL表位是天然抗GAL抗体的配体，其构成类似于人类中的1％免疫球蛋白。在施用疫苗后呈现α-加仑表位，抗GA1在疫苗接种位点与这些表位结合，并用疫苗形成免疫复合物。这些免疫复合物针对APC的APC靶向广泛摄取，其作为在APC上的APC上的FC受体的结合的结果。这种抗Gal介导的APC有效吸收疫苗的疫苗导致抗病毒免疫应答的10-200倍，并在致命的活性流感病毒攻击后8倍的存活率，而不是缺乏alpha-gal的疫苗表位。建议，用于呈现α-GAL表层的糖尿病屏蔽的糖类链中的碳水化合物链中的碳水化合物链的糖化链将对疫苗疗效具有类似的扩增作用。 α-Gal表位合成冠状病毒疫苗可以通过重组α1,3galactosyltransferase来实现，在具有高α1,3galactosyl转移酶活性的细胞中的病毒复制由于具有α1,3galactosyl转移酶基因的几份细胞的稳定转染（ GGTA1），或通过通过含有该基因的复制缺陷腺病毒进行宿主细胞进行转导。此外，在含有相应的糖基转移酶的糖型酵母或细菌表达系统中，可以在糖烷基罩上呈现多个α-加仑表达的重组S蛋白。呈现α-加仑表位的预期Covid-19疫苗可以提供比缺乏该表位的疫苗的更好的保护，因为APC增加。 （c）2020作者。 elsevier有限公司出版

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