Thongkum Weeraya, Thongheang Kanyarat, Tayapiwatana Chatchai
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Curr Issues Mol Biol. 2022 Jun 29;44(7):2842-2855. doi: 10.3390/cimb44070195.
Concerns over vaccine efficacy after the emergence of the SARS-CoV-2 Delta variant prompted revisiting the vaccine design concepts. Monoclonal antibodies (mAbs) have been developed to identify the neutralizing epitopes on spike protein. It has been confirmed that the key amino acid residues in epitopes that induce the formation of neutralizing antibodies do not have to be on the receptor-binding domain (RBD)- angiotensin-converting enzyme 2 (ACE2) contact surface, and may be conformationally hidden. In addition, this epitope is tolerant to amino acid mutations of the Delta variant. The antibody titers against RBD in health care workers in Thailand receiving two doses of CoronaVac, followed by a booster dose of BNT162b2, were significantly increased. The neutralizing antibodies against the Delta variant suggest that the overall neutralizing antibody level against the Wuhan strain, using the NeutraLISA, was consistent with the levels of anti-RBD antibodies. However, individuals with moderate anti-RBD antibody responses have different levels of a unique antibody population competing with a cross-neutralizing mAb clone, 40591-MM43, determined by in-house competitive ELISA. Since 40591-MM43 mAb indicates cross-neutralizing activity against the Delta variant, this evidence implies that the efficiency of the vaccination regimen should be improved to facilitate cross-protective antibodies against Delta variant infections. The RBD epitope recognized by 40591-MM43 mAb is hidden in the close state.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）Delta变异株出现后，对疫苗效力的担忧促使人们重新审视疫苗设计理念。已研发出单克隆抗体（mAb）来识别刺突蛋白上的中和表位。已证实，诱导中和抗体形成的表位中的关键氨基酸残基不一定位于受体结合域（RBD）-血管紧张素转换酶2（ACE2）接触表面，可能处于构象隐藏状态。此外，该表位对Delta变异株的氨基酸突变具有耐受性。在泰国，接受两剂科兴疫苗，随后一剂BNT162b2加强针的医护人员中，针对RBD的抗体滴度显著增加。针对Delta变异株的中和抗体表明，使用中和抗体检测试剂盒（NeutraLISA），针对武汉毒株的总体中和抗体水平与抗RBD抗体水平一致。然而，通过内部竞争性酶联免疫吸附测定法（ELISA）测定，具有中等抗RBD抗体反应的个体中，与一种交叉中和mAb克隆40591-MM43竞争的独特抗体群体水平有所不同。由于40591-MM43 mAb显示出对Delta变异株的交叉中和活性，这一证据表明应改进疫苗接种方案的效率，以促进产生针对Delta变异株感染的交叉保护性抗体。40591-MM43 mAb识别的RBD表位在紧密状态下处于隐藏状态。
