加拿大儿童医院研究所Jean-Philippe Julien，荷兰医学微生物学系Teun Bousema和Matthijs M. Jore共同合作，近期取得重要工作进展。他们研究发现来自自然暴露个体的强效传播阻断单克隆抗体靶向恶性疟原虫Pfs230上的保守表位。相关研究成果2023年2月14日在线发表于《免疫学》杂志上。

据介绍，Pfs230对恶性疟原虫向蚊子传播至关重要，是最先进的疟疾传播阻断疫苗候选疫苗的靶向蛋白。先前对Pfs230上功能表位的理解是基于亚单位免疫诱导的两种具有中等传播减少活性（TRA）的单克隆抗体（mAb）。

研究人员筛选了两个具有血清TRA的自然暴露个体的B细胞库，并从16个Pfs230结构域1特异性mAb中鉴定出5个有效的mAb。与Pfs230结构域1结合的三种有效和三种低活性抗体的结构揭示了四种不同的表位。来自自然感染的高效mAb识别出恶性疟原虫分离株中高度保守的一个共同构象表位，而来自自然感染或免疫的TRA可以忽略不计的抗体可以识别三个不同的位点。

总之，这一研究提供了描述恶性疟原虫TRA的分子蓝图，通过对比自然暴露和疫苗接种引起的有效和无功能表位。

附：英文原文

Title: Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230

Author: Danton Ivanochko, Amanda Fabra-García, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Jocelyn Newton, Anthony Semesi, Marloes de Bruijni, Judith Bolscher, Jordache Ramjith, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Shwu-Maan Lee, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Matthijs M. Jore, Jean-Philippe Julien

Issue&Volume: 2023/02/14

Abstract: Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine candidate. Prior understanding of functional epitopes on Pfs230 is based on two monoclonal antibodies (mAbs) with moderate transmission-reducing activity (TRA), elicited from subunit immunization. Here, we screened the B cell repertoire of two naturally exposed individuals possessing serum TRA and identified five potent mAbs from sixteen Pfs230 domain-1-specific mAbs. Structures of three potent and three low-activity antibodies bound to Pfs230 domain 1 revealed four distinct epitopes. Highly potent mAbs from natural infection recognized a common conformational epitope that is highly conserved across P. falciparum field isolates, while antibodies with negligible TRA derived from natural infection or immunization recognized three distinct sites. Our study provides molecular blueprints describing P. falciparum TRA, informed by contrasting potent and non-functional epitopes elicited by natural exposure and vaccination.

DOI: 10.1016/j.immuni.2023.01.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00023-7