近日，英国牛津大学教授Simon J. Draper及其小组发现了减缓红细胞入侵的人体抗体会增强中和疟疾的抗体。相关论文于2019年6月13日发表于国际顶尖学术期刊《细胞》杂志上。

课题组从接有基于PfRH5疫苗的首次临床试验接种者的外周血B细胞中，分离出一组针对PfRH5的人体单克隆抗体(mAbs)。随后，该课题组研究人员从中确定了一个具有中和活性的单克隆抗体子集，它们能够与三个不同的位点结合。同时确定了另一个没有功能，甚至对中和抗体是拮抗的单克隆抗体子集。该研究组还鉴定了这组新的非中和抗体的抗原表位，这些抗体显著降低了裂殖子对红细胞的侵袭速度，进而增强了所有中和PfRH5抗体的效果，以及与靶向其它疟疾侵袭蛋白的抗体产生协同作用。他们的研究结果为以结构为导向的疫苗开发，如何最大限度地提高抗体对血源性疟疾的疗效，提供了一个新的路线图。

据了解，恶性疟原虫网织红细胞结合蛋白同源蛋白5 (PfRH5)是下一代抗疟疾病红内期疫苗研发的主要靶标。然而，关于人类抗体是如何对这种抗原产生功能性免疫的，人们对此知之甚少。

附：英文原文

Title: Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Author: Daniel G.W. Alanine, Doris Quinkert, Rasika Kumarasingha, Paul R. Gilson, Matthew K. Higgins, Simon J. Draper, et al.

Issue&Volume: Jun 27, 2019 Volume 178Issue 1

Abstract: The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.

DOI: https://doi.org/10.1016/j.cell.2019.05.025

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30553-7