Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy.
Department of Pharmacological and Biomolecular Sciences DiSFeB, University of Milan, Milan, Italy.
Nat Commun. 2022 Jun 13;13(1):3375. doi: 10.1038/s41467-022-31115-8.
SARS-CoV-2 vaccines, administered to billions of people worldwide, mitigate the effects of the COVID-19 pandemic, however little is known about the molecular basis of antibody cross-protection to emerging variants, such as Omicron BA.1, its sublineage BA.2, and other coronaviruses. To answer this question, 276 neutralizing monoclonal antibodies (nAbs), previously isolated from seronegative and seropositive donors vaccinated with BNT162b2 mRNA vaccine, were tested for neutralization against the Omicron BA.1 and BA.2 variants, and SARS-CoV-1 virus. Only 14.2, 19.9 and 4.0% of tested antibodies neutralize BA.1, BA.2, and SARS-CoV-1 respectively. These nAbs recognize mainly the SARS-CoV-2 receptor binding domain (RBD) and target Class 3 and Class 4 epitope regions on the SARS-CoV-2 spike protein. Interestingly, around 50% of BA.2 nAbs did not neutralize BA.1 and among these, several targeted the NTD. Cross-protective antibodies derive from a variety of germlines, the most frequents of which were the IGHV1-58;IGHJ3-1, IGHV2-5;IGHJ4-1 and IGHV1-69;IGHV4-1. Only 15.6, 20.3 and 7.8% of predominant gene-derived nAbs elicited against the original Wuhan virus cross-neutralize Omicron BA.1, BA.2 and SARS-CoV-1 respectively. Our data provide evidence, at molecular level, of the presence of cross-neutralizing antibodies induced by vaccination and map conserved epitopes on the S protein that can inform vaccine design.
SARS-CoV-2 疫苗已在全球范围内为数以亿计的人接种，减轻了 COVID-19 大流行的影响，但人们对抗体对新兴变异体（如奥密克戎 BA.1、其亚谱系 BA.2 和其他冠状病毒）的交叉保护的分子基础知之甚少。为了回答这个问题，我们测试了 276 种中和单克隆抗体（nAb），这些抗体先前从接种 BNT162b2 mRNA 疫苗的血清阴性和血清阳性供体中分离出来，用于中和奥密克戎 BA.1 和 BA.2 变体以及 SARS-CoV-1 病毒。只有 14.2%、19.9%和 4.0%的测试抗体分别中和 BA.1、BA.2 和 SARS-CoV-1。这些 nAb 主要识别 SARS-CoV-2 的受体结合域（RBD），并靶向 SARS-CoV-2 刺突蛋白上的第 3 类和第 4 类表位区域。有趣的是，约 50%的 BA.2 nAb 不能中和 BA.1，其中一些靶向 NTD。交叉保护抗体源自多种胚系，最常见的是 IGHV1-58；IGHJ3-1、IGHV2-5；IGHJ4-1 和 IGHV1-69；IGHV4-1。针对原始武汉病毒产生的主要基因衍生 nAb 中，只有 15.6%、20.3%和 7.8%分别交叉中和奥密克戎 BA.1、BA.2 和 SARS-CoV-1。我们的数据提供了证据，证明了疫苗接种诱导的交叉中和抗体的存在，并绘制了 S 蛋白上的保守表位，这可以为疫苗设计提供信息。
