呼吸道合胞病毒预测 CD4 和 CD8 T 细胞表位的实验研究。

Experimental trials of predicted CD4 and CD8 T-cell epitopes of respiratory syncytial virus.

机构信息

Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.

School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, China.

出版信息

Front Immunol. 2024 Apr 2;15:1349749. doi: 10.3389/fimmu.2024.1349749. eCollection 2024.

DOI:10.3389/fimmu.2024.1349749

PMID:38629077

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11018974/

Abstract

BACKGROUND

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.

METHODS

We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4 and CD8 T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through and studies involving healthy and diseased animal models.

RESULTS

For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8) epitope of the F protein showed significant results of white blood cells (19.72 × 10 cells/μl), neutrophils (6.01 × 10 cells/μl), lymphocytes (12.98 × 10 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4) of the F protein substantially induced white blood cells (27.08 × 10 cells/μl), neutrophils (6.58 × 10 cells/μl), lymphocytes (16.64 × 10 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.

CONCLUSION

In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

摘要

背景

呼吸道合胞病毒（RSV）是全世界婴幼儿下呼吸道感染（LRTIs）最常见的病因，也是老年人下呼吸道感染的重要病因。目前已有针对 RSV 的治疗方法和 FDA 批准的疫苗，但这些方法只能减轻感染的严重程度，建议婴儿和老年人使用。

方法

我们专注于开发一种广谱疫苗，该疫苗能够激活免疫系统，直接对抗 RSV。本研究的目的是使用免疫信息学方法鉴定 RSV 疫苗的 CD4 和 CD8 T 细胞表位。这些肽的疗效通过涉及健康和患病动物模型的和研究得到了验证。

结果

对于每一种主要组织相容性复合体（MHC）I 类和 II 类，我们发现 RSV 蛋白的 F、G 和 SH 蛋白有三个表位，其抗原评分>0.5，预测 SVM 评分<5。在 RSV A2 株 19f 感染前后，我们在雌性 BALB/c 小鼠上对这些肽进行了实验验证。我们发现，F 蛋白的 3RVMHCI（CD8）表位在第二次加强剂量为 10μg 时，与对照组相比，白细胞（19.72×10 个细胞/μl）、中性粒细胞（6.01×10 个细胞/μl）、淋巴细胞（12.98×10 个细胞/μl）、IgG 抗体（36.9μg/ml）、IFN-γ（86.96ng/L）和颗粒酶 B（691.35pg/ml）显著增加。同样，F 蛋白的 4RVMHCII（CD4）表位也显著诱导了白细胞（27.08×10 个细胞/μl）、中性粒细胞（6.58×10 个细胞/μl）、淋巴细胞（16.64×10 个细胞/μl）、IgG 抗体（46.13μg/ml）、IFN-γ（96.45ng/L）和颗粒酶 B（675.09pg/ml）的产生。研究表明，在第 45 天，4RVMHCII 可在血清中产生与感染病毒的小鼠相当水平的抗体。4RVMHCII 在挑战的第四天也比感染前阶段产生了更高的 IFN-γ 和 IL-2 分泌。