巴西René Rachou研究所Caroline Junqueira团队的研究开发出了跨阶段、跨物种疟疾CD8+ T细胞抗原的鉴定。2026年7月1日出版的《自然》杂志发表了这项成果。

该研究组以前报道过网织红细胞感染间日疟原虫表达人白细胞抗原I类（HLA-I），使CD8+ T细胞能够识别和杀死疟原虫。

在这里，该课题组人员主题免疫肽组学鉴定疟原虫抗原衍生肽由HLA-I在感染的网织细胞。研究组鉴定了453个独特的肽，映射到166个蛋白质。75种抗原是恒温蛋白，在寄生虫生命周期的多个阶段组成性表达，并且在疟原虫物种之间高度保守。不同的个体通过相同或不同的HLA-A、HLA-B和HLA-C等位基因以及非经典的HLA-E等位基因呈现相同的肽。新鉴定表位的抗原性已在间日疟原虫感染者和恶性疟原虫感染者样本中得到验证。

此外，在感染疟原虫或免疫减毒疟原虫后，在非人类灵长类动物的血液和肝脏中观察到对这些抗原的T细胞反应。两种抗原也在啮齿类动物中诱导保护性CD8+ T细胞介导的免疫。因此，这些抗原有可能成为跨阶段和跨物种疟疾疫苗的主题。

据悉，疟疾疫苗开发的一个主要限制是缺乏经过验证的T细胞表位靶标。恶性疟原虫是非洲影响人类的最普遍的疟疾寄生虫，而间日疟原虫分布更广，是美洲和亚洲导致疟疾的主要物种。间日疟原虫只感染外周血网织细胞，网织细胞保留RNA和宿主蛋白质合成能力。

附：英文原文

Title: Identification of cross-stage, cross-species malaria CD8+ T cell antigens

Author: Barbosa, Camila R. R., de Lacerda, Luna B., Bettencourt, Paulo J. G., Morrow, David, Pereira, Dhelio B., Aleshnick, Maya, Mitchell, Julie L., Poulton, Nicholas C., Gomes, Cristopher, Cordeiro, Ldia P. B., Doumbia, Kadia, Ntalla, Christina, Arama, Charles, Zhao, Zezhou, Maia, Guilherme C., Almeida, Gregrio G., Schrimpf, Marie Rose, Hart, Thalia F., Haumpy, Derek, Medeiros-Rodrigues, Beatriz C., Costa, Camila M., Nicastri, Annalisa, Gilbride, Roxanne M., Schell, John B., Kirtley, Payton, Antonelli, Lis R. V., Gaiha, Gaurav D., Hansen, Scott G., Lieberman, Judy, Gazzinelli, Ricardo T., Niangaly, Moussa, Woodford, John, Goldberg, Joel, Frh, Klaus, Portugal, Silvia, Duffy, Patrick E., Ternette, Nicola, Wilder, Brandon, Hill, Adrian V. S., Junqueira, Caroline

Issue&Volume: 2026-07-01

Abstract: A major limitation on the development of a malaria vaccine is the lack of validated T cell epitope targets. Plasmodium falciparum is the most prevalent malaria parasite affecting humans in Africa, whereas Plasmodium vivax is more widespread and is the main species that causes malaria in the Americas and Asia1. P.vivax exclusively infects peripheral-blood reticulocytes, which retain RNA and the capacity for host protein synthesis2. We previously reported that reticulocytes infected with P.vivax express human leukocyte antigen class I (HLA-I), which enables recognition and killing of the parasite by CD8+ T cells3. Here we use immunopeptidomics to identify Plasmodium-antigen-derived peptides presented by HLA-I on infected reticulocytes. We identified 453 unique peptides, mapping to 166 proteins. Seventy-five antigens were housekeeping proteins that are constitutively expressed at multiple stages of the parasite’s life cycle and are highly conserved between Plasmodium species. Identical peptides were presented in different individuals by the same or distinct HLA-A, HLA-B and HLA-C alleles, as well as by the non-classical HLA-E allele. The antigenicity of the newly identified epitopes was validated in samples from both P.vivax-infected and P.falciparum-infected individuals. Furthermore, T cell responses to several of these antigens were observed in the blood and liver of non-human primates after infection with Plasmodium or immunization with attenuated parasites. Two antigens also induced protective CD8+ T cell-mediated immunity in rodents. Thus, these antigens have the potential for use in a cross-stage and cross-species malaria vaccine.

DOI: 10.1038/s41586-026-10730-1

Source: https://www.nature.com/articles/s41586-026-10730-1

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com/

投稿链接：http://www.nature.com/authors/submit_manuscript.html