Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, United States.
Front Immunol. 2021 Mar 9;12:637651. doi: 10.3389/fimmu.2021.637651. eCollection 2021.
As COVID-19 cases continue to rise, it is imperative to learn more about antibodies and T-cells produced against the causative virus, SARS-CoV-2, in order to guide the rapid development of therapies and vaccines. While much of the current antibody and vaccine research focuses on the receptor-binding domain of S1, a less-recognized opportunity is to harness the potential benefits of the more conserved S2 subunit. Similarities between the spike proteins of both SARS-CoV-2 and HIV-1 warrant exploring S2. Possible benefits of employing S2 in therapies and vaccines include the structural conservation of S2, extant cross-reactive neutralizing antibodies in populations (due to prior exposure to common cold coronaviruses), the steric neutralization potential of antibodies against S2, and the stronger memory B-cell and T-cell responses. More research is necessary on the effect of glycans on the accessibility and stability of S2, SARS-CoV-2 mutants that may affect infectivity, the neutralization potential of antibodies produced by memory B-cells, cross-reactive T-cell responses, antibody-dependent enhancement, and antigen competition. This perspective aims to highlight the evidence for the potential advantages of using S2 as a target of therapy or vaccine design.
随着 COVID-19 病例的持续增加，了解更多针对致病病毒 SARS-CoV-2 产生的抗体和 T 细胞是至关重要的，以便指导治疗方法和疫苗的快速开发。虽然当前的大部分抗体和疫苗研究都集中在 S1 的受体结合域上，但利用 S2 亚单位的潜在优势是一个较少被关注的机会。SARS-CoV-2 和 HIV-1 的刺突蛋白之间存在相似性，这使得探索 S2 成为必要。在治疗方法和疫苗中使用 S2 的可能好处包括 S2 的结构保守性、人群中存在的交叉反应性中和抗体（由于先前暴露于普通感冒冠状病毒）、针对 S2 的抗体的空间中和潜力，以及更强的记忆 B 细胞和 T 细胞反应。需要进一步研究糖基对 S2 的可及性和稳定性的影响、可能影响传染性的 SARS-CoV-2 突变体、记忆 B 细胞产生的抗体的中和潜力、交叉反应性 T 细胞反应、抗体依赖性增强和抗原竞争。本观点旨在强调使用 S2 作为治疗或疫苗设计靶点的潜在优势的证据。
