美国国立卫生研究院Niraj H. Tolia和Patrick E. Duffy共同合作，近期取得重要工作进展。他们绘制了Pfs230D1的人类抗体表位图谱，源自对接种疟疾传播阻断疫苗个体的分析。相关研究成果2023年2月14日在线发表于《免疫》杂志上。

据介绍，Pfs230结构域1（Pfs230D1）是一种先进的疟疾传播阻断疫苗抗原，在临床试验中显示出高功能活性。然而，目前还没有定义传输阻断活动的结构和功能相关性。

研究人员对一组人单克隆抗体 (hmAb) 进行了表征，这些抗体是在用Pfs230D1免疫的疫苗接种者中产生的。这些hmAb表现出不同的传输减少活性，但都以纳摩尔亲和力与Pfs230D1结合。研究人员编译了17个hmAb和9个hmAb复合物的表位结合数据，构建了一个高分辨率的表位图，并揭示了有效的减少传输的hmAb结合在Pfs230D1的一面，而无效的hmAb结合在相反的一面。Pfs230D1D2的结构表明，无效的传播减少表位被第二结构域阻断。hmAb表位图描绘了两个hmAb组合，具有极高的效力和减少传播的活性。

总之，这项工作为增强免疫原的基于结构的设计提供了高分辨率指南，并为测量传播减少反应的诊断提供了信息。

附：英文原文

Title: A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine

Author: Wai Kwan Tang, Camila H. Coelho, Kazutoyo Miura, Bergeline C. Nguemwo Tentokam, Nichole D. Salinas, David L. Narum, Sara A. Healy, Issaka Sagara, Carole A. Long, Patrick E. Duffy, Niraj H. Tolia

Issue&Volume: 2023/02/14

Abstract: Pfs230 domain 1 (Pfs230D1) is an advanced malaria transmission-blocking vaccine antigendemonstrating high functional activity in clinical trials. However, the structuraland functional correlates of transmission-blocking activity are not defined. Here,we characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccineesimmunized with Pfs230D1. These hmAbs exhibited diverse transmission-reducing activity,yet all bound to Pfs230D1 with nanomolar affinity. We compiled epitope-binning datafor seventeen hmAbs and structures of nine hmAbs complexes to construct a high-resolutionepitope map and revealed that potent transmission-reducing hmAbs bound to one faceof Pfs230D1, while non-potent hmAbs bound to the opposing side. The structure of Pfs230D1D2revealed that non-potent transmission-reducing epitopes were occluded by the seconddomain. The hmAb epitope map delineated binary hmAb combinations that synergized forextremely high-potency, transmission-reducing activity. This work provides a high-resolutionguide for structure-based design of enhanced immunogens and informs diagnostics thatmeasure the transmission-reducing response.

DOI: 10.1016/j.immuni.2023.01.012

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00022-5