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在小鼠模型中对 PvCyRPA、PvCelTOS 和 Pvs25 嵌合重组蛋白的免疫原性研究。

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of in murine model.

机构信息

Immunoparasitology Laboratory, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.

Hantaviruses and Rickettsioses Laboratory, IOC, Fiocruz, Rio de Janeiro, Brazil.

出版信息

Front Immunol. 2024 Jun 19;15:1392043. doi: 10.3389/fimmu.2024.1392043. eCollection 2024.

DOI:10.3389/fimmu.2024.1392043
PMID:38962015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11219565/
Abstract

In the Americas, is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.

摘要

在美洲, 是疟疾的主要病原体,疟疾是一种使人虚弱且具有重要经济意义的疾病。由于疟原虫生活周期的复杂性,含有多种在不同寄生虫阶段表达的抗原的疫苗制剂可能是一种有效的方法。基于这一点,我们之前设计并构建了一种嵌合重组蛋白 PvRMC-1,由 PvCyRPA、PvCelTOS 和 Pvs25 表位组成。这种嵌合蛋白强烈地被来自巴西亚马逊暴露人群的天然获得的抗体所识别。然而,我们并没有研究 PvRMC-1 诱导的免疫反应。因此,在这项工作中,我们评估了该嵌合抗原在三种不同佐剂中的免疫原性:Stimune、AddaVax 或氢氧化铝(Al(OH)3)在 BALB/c 小鼠中的应用。我们的结果表明,该嵌合蛋白 PvRMC-1 能够在所有三种制剂中产生体液和细胞反应。抗体识别全长 PvRMC-1 和来自 PvCyRPA、PvCelTOS 和 Pvs25 的线性 B 细胞表位。此外,小鼠的脾细胞被激活,对 PvCelTOS 和 PvCyRPA 肽表位产生 IFN-γ,证实了抗原中的 T 细胞表位。虽然氢氧化铝表现出显著的细胞反应,但 Stimune 和 Addavax 诱导了更全面的免疫反应,包括细胞和体液成分。因此,我们的研究结果表明 PvRMC-1 可能是一种有前途的多阶段疫苗候选物,可以进一步推进临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/94ab479e5b9b/fimmu-15-1392043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/9fd95ce9d2ce/fimmu-15-1392043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/c0ede431b7b3/fimmu-15-1392043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/6fda8bc1e327/fimmu-15-1392043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/c5d861b09f27/fimmu-15-1392043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/94ab479e5b9b/fimmu-15-1392043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/9fd95ce9d2ce/fimmu-15-1392043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/c0ede431b7b3/fimmu-15-1392043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/6fda8bc1e327/fimmu-15-1392043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/c5d861b09f27/fimmu-15-1392043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee30/11219565/94ab479e5b9b/fimmu-15-1392043-g005.jpg

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