美国哈佛大学Facundo D. Batista等研究人员合作发现，在人源化小鼠模型中接种疫苗可产生高度保护性的PfCSP靶向抗疟疾抗体。2021年11月16日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员表示，重复抗原，如恶性疟原虫环子孢子蛋白（PfCSP），同时利用序列简并和结构多样性来逃避免疫反应。研究已经确定了一些有效预防疟疾感染的PfCSP定向抗体，包括CIS43，但如何改进这些重复定向抗体一直不清楚。

研究人员设计了一个人源化的小鼠模型，其中B细胞表达推测的人类种系CIS43（iGL-CIS43）B细胞受体，并使用疫苗接种和生物信息学分析来获得具有改进的保护能力的变体CIS43抗体。其中一个这样的抗体，iGL-CIS43.D3，比目前同类最佳的PfCSP定向抗体的效力要大得多。研究人员发现，在招募iGL-CIS43 B细胞到生发中心方面，用交界处的表位肽接种比全长的PfCSP更有效。结构-功能分析显示，多个体细胞高突变可组合性地改善保护。因此，这种小鼠模型可用于了解疫苗免疫原和开发高度有效的抗疟疾抗体。

附：英文原文

Title: Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies

Author: Sven Kratochvil, Chen-Hsiang Shen, Ying-Cing Lin, Kai Xu, Usha Nair, Lais Da Silva Pereira, Prabhanshu Tripathi, Johan Arnold, Gwo-Yu Chuang, Eleonora Melzi, Arne Schn, Baoshan Zhang, Marlon Dillon, Brian Bonilla, Barbara J. Flynn, Kathrin H. Kirsch, Neville K. Kisalu, Patience K. Kiyuka, Tracy Liu, Li Ou, Marie Pancera, Reda Rawi, Mateo Reveiz, Kareen Seignon, Lawrence T. Wang, Michael T. Waring, John Warner, Yongping Yang, Joseph R. Francica, Azza H. Idris, Robert A. Seder, Peter D. Kwong, Facundo D. Batista

Issue&Volume: 2021-11-16

Abstract: Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.

DOI: 10.1016/j.immuni.2021.10.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00454-4

期刊信息

Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：21.522

官方网址：https://www.cell.com/immunity/home

投稿链接：https://www.editorialmanager.com/immunity/default.aspx