Huamin Medicine Co Ltd., Zhuhai, China.
Wolfson Institute for Biomedical Research, University College London, London, UK.
J Immunol Res. 2020 Oct 17;2020:9465398. doi: 10.1155/2020/9465398. eCollection 2020.
This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.
新的十年以由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 COVID-19 全球大流行拉开序幕，这场大流行引发了全球卫生危机和经济衰退。科学家和临床医生一直在争分夺秒地寻找 COVID-19 的治疗方法。重新利用已批准的药物、开发疫苗和使用被动免疫是对抗 COVID-19 的三种主要治疗方法。鸡免疫球蛋白 Y（IgY）有可能被用作针对呼吸道感染的中和抗体，其优点包括高亲和力、低不良免疫反应风险以及通过鼻腔内给药易于局部递送。在这项研究中，我们在鸡中针对 SARS-CoV-2 的刺突（S）蛋白产生抗体，并从蛋黄中提取 IgY（称为 IgY-S）。IgY-S 对 SARS-CoV-2 S 表现出高免疫反应性，通过表位作图，我们在 SARS-CoV-2 S 中发现了 IgY-S 的五个线性表位，其中两个与 SARS-CoV S 交叉反应。值得注意的是，鉴定出的表位之一 SIIAYTMSL 部分重叠 SARS-CoV-2 S 中的 S1/S2 切割区域，并且位于 S 三聚体的表面，靠近 S1/S2 切割位点。因此，该位置的抗体结合可能会物理阻止蛋白酶进入 S1/S2 切割位点，从而阻碍 S1/S2 的蛋白水解切割，这对于随后的病毒-细胞膜融合和病毒细胞进入至关重要。因此，探索使用 IgY-S 或表位 SIIAYTMS 特异性 IgY 作为预防或治疗 SARS-CoV-2 感染的中和抗体的可行性是值得的。
