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源自人嗜T淋巴细胞病毒1型(HTLV-1)蛋白并与明矾佐剂结合的重组GPEHT融合蛋白在小鼠中诱导出高免疫反应。

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice.

作者信息

Jahantigh Hamid Reza, Stufano Angela, Koohpeyma Farhad, Nikbin Vajihe Sadat, Shahosseini Zahra, Lovreglio Piero

机构信息

Interdisciplinary Department of Medicine, Section of Occupational Medicine, University of Bari, 70214 Bari, Italy.

Department of Pathology, Faculty of Medicine, Emory University, Atlanta, GA 30033, USA.

出版信息

Vaccines (Basel). 2023 Jan 3;11(1):115. doi: 10.3390/vaccines11010115.

DOI:10.3390/vaccines11010115
PMID:36679960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9865465/
Abstract

The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the , , , , and proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.

摘要

人类T细胞白血病病毒1型(HTLV-1)是一种正链单链RNA病毒,属于δ逆转录病毒科。因此,一种能被B细胞和T细胞识别的候选疫苗是产生持久免疫反应的良好候选者。此外,GPEHT蛋白是一种基于HTLV-1的、、、和蛋白设计的多表位蛋白。在研发一种合适且有效的抗HTLV-1疫苗时,对一种设计蛋白(GPEHT)与明矾佐剂的配方进行了选择。在本研究中,我们评估了一种多表位候选疫苗刺激针对HTLV-1的免疫反应的潜力。在评估所刺激的免疫反应类型时,分析了总IgG、IgG1和IgG2a同种型以及与Th1(IFN-γ)、Th2(IL-4)和Th17(IL-17)相关的细胞因子。结果表明,接受GPEHT蛋白与明矾佐剂的小鼠中特定抗血清(总IgG)比PBS+明矾对照组中的小鼠升高得更多。用我们的嵌合蛋白进行皮下接种可促进高水平的IgG1和IgG2a同种型。此外,接受GPEHT蛋白的小鼠脾细胞刺激后,IFN-γ、IL-4和IL-17水平显著升高。免疫原性分析表明,GPEHT候选疫苗可产生体液免疫和细胞介导的免疫反应。最终,本研究表明,用明矾佐剂研发的GPEHT蛋白很快可被视为一种前瞻性疫苗,以更准确地评估其对HTLV-1的保护效力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/7a3855383c8b/vaccines-11-00115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/db60372ed4cc/vaccines-11-00115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/f18f8608e084/vaccines-11-00115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/8e541c0dd3be/vaccines-11-00115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/8bc96ec433aa/vaccines-11-00115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/7a3855383c8b/vaccines-11-00115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/db60372ed4cc/vaccines-11-00115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/f18f8608e084/vaccines-11-00115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/8e541c0dd3be/vaccines-11-00115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/8bc96ec433aa/vaccines-11-00115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/9865465/7a3855383c8b/vaccines-11-00115-g005.jpg

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