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鉴定亚蛋白质组的免疫显性蛋白作为抗利什曼病的泛特异性疫苗靶点。

Identification of Immunodominant Proteins of the SubProteome as Pan-Specific Vaccine Targets against Leishmaniasis.

作者信息

Jesus-Oliveira Prisciliana, Silva-Couto Luzinei, Pinho Nathalia, Da Silva-Ferreira André Teixeira, Saboia-Vahia Leonardo, Cuervo Patricia, Da-Cruz Alda Maria, Gomes-Silva Adriano, Pinto Eduardo Fonseca

机构信息

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.

Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.

出版信息

Vaccines (Basel). 2023 Jun 21;11(7):1129. doi: 10.3390/vaccines11071129.

Abstract

is a wide-spectrum disease caused by parasites from genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that causes benign disease and its antigens induce well-modulated immune responses in vitro. In this work we aimed to identify the immunodominant proteins present in the soluble extract of (sLnAg) as candidates for composing a pan-specific anti-leishmaniasis vaccine. After immunoblotting using cured patients of cutaneous leishmaniasis sera and proteomics approaches, we identified a group of antigenic proteins from the sLnAg. In silico analyses allowed us to select mildly similar proteins to the host; in addition, we evaluated the binding potential and degree of promiscuity of the protein epitopes to HLA molecules and to B-cell receptors. We selected 24 immunodominant proteins from a sub-proteome with 328 proteins. Homology analysis allowed the identification of 13 proteins with the most orthologues among seven species. This work demonstrated the potential of these proteins as promising vaccine targets capable of inducing humoral and cellular pan-specific immune responses in humans, which may in the future contribute to the control of leishmaniasis.

摘要

是由该属寄生虫引起的一种广谱疾病。利什曼病长期临床治愈后建立的良好调节的免疫反应可代表疫苗的标准要求。先前的研究表明,会引发良性疾病,其抗原在体外可诱导良好调节的免疫反应。在这项工作中,我们旨在鉴定存在于(sLnAg)可溶性提取物中的免疫显性蛋白,作为组成泛特异性抗利什曼病疫苗的候选物。使用皮肤利什曼病治愈患者血清进行免疫印迹和蛋白质组学方法后,我们从sLnAg中鉴定出一组抗原蛋白。通过计算机分析,我们能够选择与宿主轻度相似的蛋白质;此外,我们评估了蛋白质表位与HLA分子和B细胞受体的结合潜力和混杂程度。我们从一个包含328种蛋白质的亚蛋白质组中选择了24种免疫显性蛋白。同源性分析使我们能够在七种物种中鉴定出具有最多直系同源物的13种蛋白质。这项工作证明了这些蛋白质作为有前景的疫苗靶点的潜力,能够在人类中诱导体液和细胞泛特异性免疫反应,这在未来可能有助于控制利什曼病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce78/10386316/d89a94c37657/vaccines-11-01129-g001.jpg

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