Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
Universidad Santo Tomás, Bogotá, Colombia.
Front Immunol. 2021 Sep 3;12:724060. doi: 10.3389/fimmu.2021.724060. eCollection 2021.
Thirty-five peptides selected from functionally-relevant SARS-CoV-2 spike (S), membrane (M), and envelope (E) proteins were suitably modified for immunising MHC class II (MHCII) DNA-genotyped monkeys and matched with HLA-DRβ1* molecules for use in humans. This was aimed at producing the first minimal subunit-based, chemically-synthesised, immunogenic molecules (COLSARSPROT) covering several HLA alleles. They were predicted to cover 48.25% of the world's population for 6 weeks (short-term) and 33.65% for 15 weeks (long-lasting) as they induced very high immunofluorescent antibody (IFA) and ELISA titres against S, M and E parental native peptides, SARS-CoV-2 neutralising antibodies and host cell infection. The same immunological methods that led to identifying new peptides for inclusion in the COLSARSPROT mixture were used for antigenicity studies. Peptides were analysed with serum samples from patients suffering mild or severe SARS-CoV-2 infection, thereby increasing chemically-synthesised peptides' potential coverage for the world populations up to 62.9%. These peptides' 3D structural analysis (by H-NMR acquired at 600 to 900 MHz) suggested structural-functional immunological association. This first multi-protein, multi-epitope, minimal subunit-based, chemically-synthesised, highly immunogenic peptide mixture highlights such chemical synthesis methodology's potential for rapidly obtaining very pure, highly reproducible, stable, cheap, easily-modifiable peptides for inducing immune protection against COVID-19, covering a substantial percentage of the human population.
从功能相关的 SARS-CoV-2 刺突 (S)、膜 (M) 和包膜 (E) 蛋白中选择了 35 个肽段,经过适当修饰后用于免疫 MHC Ⅱ类 (MHCII) DNA 基因分型的猴子,并与 HLA-DRβ1*分子匹配,用于人类。这旨在生产第一个基于最小亚基的、化学合成的、具有免疫原性的分子 (COLSARSPROT),涵盖多个 HLA 等位基因。它们预计在 6 周(短期)内覆盖世界人口的 48.25%,在 15 周(长期)内覆盖 33.65%,因为它们诱导了针对 S、M 和 E 亲本天然肽、SARS-CoV-2 中和抗体和宿主细胞感染的非常高的免疫荧光抗体 (IFA) 和 ELISA 滴度。用于确定包含在 COLSARSPROT 混合物中的新肽的相同免疫方法用于抗原性研究。用患有轻度或重度 SARS-CoV-2 感染的患者的血清样本分析肽段,从而将化学合成肽段对世界人口的潜在覆盖率提高到 62.9%。这些肽段的 3D 结构分析(通过在 600 到 900 MHz 之间获得的 H-NMR)表明结构-功能免疫关联。这种第一个多蛋白、多表位、最小亚基的、化学合成的、高度免疫原性的肽混合物突出了这种化学合成方法的潜力,可快速获得非常纯、高度重现性、稳定、廉价、易于修饰的肽,以诱导针对 COVID-19 的免疫保护,覆盖相当大比例的人类人口。