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携带HIV-1 gp160的重组病毒单纯疱疹病毒1型与HIV-1病毒样颗粒联合疫苗在BALB/c小鼠中的应答反应。

Response to HIV-1 gp160-carrying recombinant virus HSV-1 and HIV-1 VLP combined vaccine in BALB/c mice.

作者信息

Zhang Beibei, Mao Hongyan, Zhu Hongjuan, Guo Jingxia, Zhou Paul, Ma Zhenghai

机构信息

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Ürümqi, Xinjiang, China.

Unit of Antiviral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

出版信息

Front Microbiol. 2023 Mar 17;14:1136664. doi: 10.3389/fmicb.2023.1136664. eCollection 2023.

Abstract

Human immunodeficiency virus (HIV) induced AIDS causes a large number of infections and deaths worldwide every year, still no vaccines are available to prevent infection. Recombinant herpes simplex virus type 1 (HSV-1) vector-based vaccines coding the target proteins of other pathogens have been widely used for disease control. Here, a recombinant virus with HIV-1 gene integration into the internal reverse (IR) region-deleted HSV-1 vector (HSV-BAC), was obtained by bacterial artificial chromosome (BAC) technology, and its immunogenicity investigated in BALB/c mice. The result showed similar replication ability of the HSV-BAC-based recombinant virus and wild type. Furthermore, humoral and cellular immune response showed superiority of intraperitoneal (IP) administration, compared to intranasally (IN), subcutaneous (SC) and intramuscularly (IM), that evidenced by production of significant antibody and T cell responses. More importantly, in a prime-boost combination study murine model, the recombinant viruses prime followed by HIV-1 VLP boost induced stronger and broader immune responses than single virus or protein vaccination in a similar vaccination regimen. Antibody production was sufficient with huge potential for viral clearance, along with efficient T-cell activation, which were evaluated by the enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FC). Overall, these findings expose the value of combining different vaccine vectors and modalities to improve immunogenicity and breadth against different HIV-1 antigens.

摘要

人类免疫缺陷病毒(HIV)引发的艾滋病每年在全球导致大量感染和死亡,目前仍没有可用于预防感染的疫苗。编码其他病原体靶蛋白的基于重组1型单纯疱疹病毒(HSV-1)载体的疫苗已被广泛用于疾病控制。在此,通过细菌人工染色体(BAC)技术获得了一种将HIV-1基因整合到内部反向(IR)区域缺失的HSV-1载体(HSV-BAC)中的重组病毒,并在BALB/c小鼠中研究了其免疫原性。结果显示基于HSV-BAC的重组病毒与野生型具有相似的复制能力。此外,与鼻内(IN)、皮下(SC)和肌肉内(IM)给药相比,体液和细胞免疫反应显示出腹腔内(IP)给药的优势,这通过显著的抗体和T细胞反应得以证明。更重要的是,在一项初免-加强联合研究小鼠模型中,在相似的疫苗接种方案下,先用重组病毒初免然后用HIV-1病毒样颗粒(VLP)加强诱导的免疫反应比单一病毒或蛋白疫苗接种更强、更广泛。通过酶联免疫吸附测定(ELISA)和流式细胞术(FC)评估,抗体产生充足,具有巨大的病毒清除潜力,同时伴有有效的T细胞激活。总体而言,这些发现揭示了组合不同疫苗载体和方式以提高针对不同HIV-1抗原的免疫原性和广度的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9c0/10063819/8fe49767beb1/fmicb-14-1136664-g001.jpg

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