Emerging severe acute respiratory syndrome coronavirus 2 variants and their impact on immune evasion and vaccine-induced immunity.

Ramendra Pati Pandey,Sachin Kumar,D N Rao,Dablu Lal Gupta
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants harboring mutations in the structural protein, especially in the receptor binding domain (RBD) of spike protein, have raised concern about potential immune escape. The spike protein of SARS-CoV-2 plays a vital role in infection and is an important target for neutralizing antibodies. The mutations that occur in the structural proteins, especially in the spike protein, lead to changes in the virus attributes of transmissibility, an increase in disease severity, a notable reduction in neutralizing antibodies generated and thus a decreased response to vaccines and therapy. The observed multiple mutations in the RBD of the spike protein showed immune escape because it increases the affinity of spike protein binding with the ACE-2 receptor of host cells and increases resistance to neutralizing antibodies. Cytotoxic T-cell responses are crucial in controlling SARS-CoV-2 infections from the infected tissues and clearing them from circulation. Cytotoxic T cells efficiently recognized the infected cells and killed them by releasing soluble mediator's perforin and granzymes. However, the overwhelming response of T cells and, subsequently, the overproduction of inflammatory mediators during severe infections with SARS-CoV-2 may lead to poor outcomes. This review article summarizes the impact of mutations in the spike protein of SARS-CoV-2, especially mutations of RBD, on immunogenicity, immune escape and vaccine-induced immunity, which could contribute to future studies focusing on vaccine design and immunotherapy.
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新出现的严重急性呼吸系统综合征冠状病毒 2 变体及其对免疫逃避和疫苗诱导免疫的影响。
严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)变种的结构蛋白,特别是尖峰蛋白的受体结合域(RBD)发生突变,引起了人们对潜在免疫逃逸的关注。SARS-CoV-2 的尖峰蛋白在感染中起着至关重要的作用,是中和抗体的重要靶标。结构蛋白,特别是尖峰蛋白发生突变,会导致病毒的传播属性发生变化,疾病严重程度增加,产生的中和抗体明显减少,从而降低对疫苗和治疗的反应。所观察到的尖峰蛋白 RBD 的多重突变显示了免疫逃逸,因为它增加了尖峰蛋白与宿主细胞 ACE-2 受体结合的亲和力,增加了对中和抗体的抵抗力。细胞毒性 T 细胞反应对于控制受感染组织中的 SARS-CoV-2 感染并将其从血液循环中清除至关重要。细胞毒性 T 细胞能有效识别受感染的细胞,并通过释放可溶性介质穿孔素和颗粒酶杀死它们。然而,在严重感染 SARS-CoV-2 时,T 细胞的过度反应以及随后炎症介质的过度分泌可能会导致不良后果。这篇综述文章总结了 SARS-CoV-2 棘突蛋白的突变,尤其是 RBD 的突变对免疫原性、免疫逃逸和疫苗诱导免疫的影响,有助于今后以疫苗设计和免疫疗法为重点的研究。
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