Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell Rep. 2023 Apr 25;42(4):112370. doi: 10.1016/j.celrep.2023.112370. Epub 2023 Apr 7.
Understanding the human antibody response to emerging viral pathogens is key to epidemic preparedness. As the size of the B cell response to a pathogenic-virus-protective antigen is poorly defined, we perform deep paired heavy- and light-chain sequencing in Ebola virus glycoprotein (EBOV-GP)-specific memory B cells, allowing analysis of the ebolavirus-specific antibody repertoire both genetically and functionally. This approach facilitates investigation of the molecular and genetic basis for the evolution of cross-reactive antibodies by elucidating germline-encoded properties of antibodies to EBOV and identification of the overlap between antibodies in the memory B cell and serum repertoire. We identify 73 public clonotypes of EBOV, 20% of which encode antibodies with neutralization activity and capacity to protect mice in vivo. This comprehensive analysis of the public and private antibody repertoire provides insight into the molecular basis of the humoral immune response to EBOV GP, which informs the design of vaccines and improved therapeutics.
了解人体对新兴病毒病原体的抗体反应是疫情防范的关键。由于针对致病病毒保护性抗原的 B 细胞反应的规模尚未确定，我们对埃博拉病毒糖蛋白（EBOV-GP）特异性记忆 B 细胞进行深度配对的重链和轻链测序，从而能够从遗传和功能上分析埃博拉病毒特异性抗体库。这种方法通过阐明针对 EBOV 的抗体的胚系编码特性，并鉴定记忆 B 细胞和血清库中抗体之间的重叠，促进了对交叉反应性抗体进化的分子和遗传基础的研究。我们鉴定了 73 种公共的 EBOV 克隆型，其中 20％的克隆型编码具有中和活性并能够在体内保护小鼠的抗体。对公共和私人抗体库的全面分析提供了对 EBOV GP 体液免疫反应的分子基础的深入了解，为疫苗和改进的治疗方法的设计提供了信息。
