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CMVpp65 和 gH 肽-CRM197 偶联疫苗诱导 DC 成熟和有效的病毒特异性 T 细胞应答。

CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses.

机构信息

Department of Pathogenic Biology, Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China.

出版信息

Virulence. 2023 Dec;14(1):2169488. doi: 10.1080/21505594.2023.2169488.

DOI:10.1080/21505594.2023.2169488
PMID:36723437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9897769/
Abstract

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

摘要

人巨细胞病毒(HCMV)感染在全球范围内普遍存在,目前尚无许可的 HCMV 疫苗来控制它。因此,开发有效的 HCMV 疫苗是当务之急。由于其出色的免疫原性,HCMV 的关键成分磷酸蛋白 65(pp65)和糖蛋白 H(gH)是 HCMV 疫苗设计的潜在靶蛋白。在这项研究中,我们预测并筛选了与载体蛋白交叉反应物质 197(CRM197)结合的 pp65 和 gH 的 B 细胞和 T 细胞优势抗原表位,形成三种肽-CRM197 疫苗(pp65-CRM197、gH-CRM197 和 pp65-CRM197+gH-CRM197)。此外,还研究了肽-CRM197 疫苗的免疫原性及其对树突状细胞(DC)的影响。结果表明,三种肽-CRM197 疫苗可通过 p38 MAPK 信号通路诱导 DC 成熟,并促进 TNF-α和白细胞介素(IL)-6 等促炎因子的释放。同时,肽-CRM197 疫苗可有效激活 T 细胞和体液免疫,效果远优于灭活的 HCMV 疫苗。总之,我们构建了三种肽-CRM197 疫苗,可诱导多种免疫效应,为 HCMV 疫苗设计提供了新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/8ef06a0bfece/KVIR_A_2169488_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/475baf27bb4c/KVIR_A_2169488_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/6f3b1d2de526/KVIR_A_2169488_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/f789e3b1f1d4/KVIR_A_2169488_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/5c550e60a946/KVIR_A_2169488_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/d0c7eb8faf78/KVIR_A_2169488_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/8ef06a0bfece/KVIR_A_2169488_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/475baf27bb4c/KVIR_A_2169488_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/6f3b1d2de526/KVIR_A_2169488_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/f789e3b1f1d4/KVIR_A_2169488_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/5c550e60a946/KVIR_A_2169488_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/d0c7eb8faf78/KVIR_A_2169488_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d227/9897769/8ef06a0bfece/KVIR_A_2169488_F0006_OC.jpg

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