德国癌症研究所（DKFZ）Hedda Wardemann、加拿大多伦多大学Jean-Philippe Julien以及德国马克斯·普朗克感染生物学研究所Elena A. Levashina课题组合作取得新进展。他们揭示抗人疟原虫恶性疟原虫（PfCSP）环子孢子蛋白重复基序的保护性人类抗体的进化机制。2020年5月25日，《自然—医学》发表了这一成果。

通过表征由子孢子免疫诱导的200个人单克隆PfCSP抗体，他们建立了最有效的抗体结合保守（N / D）PNANPN（V / A）核心。对核心的高抗体亲和力与小鼠抗寄生虫病相关，并围绕NANP基序的识别而发展。数据表明，引发针对核心表位的高亲和力抗体反应的二代PfCSP疫苗的合理设计，将促进保护性体液免疫反应的诱导。

据悉，如动物模型所示，PfCSP的环子孢子蛋白是预防感染和疾病的抗体的主要靶标。但是，基于PfCSP的疫苗RTS、S的功效有限，需要更好地了解驱动最有效的人PfCSP抗体的发展及其目标表位鉴定的机制。

附：英文原文

Title: Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs

Author: Rajagopal Murugan, Stephen W. Scally, Giulia Costa, Ghulam Mustafa, Elaine Thai, Tizian Decker, Alexandre Bosch, Katherine Prieto, Elena A. Levashina, Jean-Philippe Julien, Hedda Wardemann

Issue&Volume: 2020-05-25

Abstract: The circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses.

DOI: 10.1038/s41591-020-0881-9

Source: https://www.nature.com/articles/s41591-020-0881-9