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针对乳腺癌的含肉瘤抗原 NY-SAR-35 表位的肽疫苗的生物信息学设计及其在 BALB/c 小鼠模型中的免疫功能评估。

Bioinformatics design of a peptide vaccine containing sarcoma antigen NY-SAR-35 epitopes against breast cancer and evaluation of its immunological function in BALB/c mouse model.

机构信息

Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

PLoS One. 2024 Jun 26;19(6):e0306117. doi: 10.1371/journal.pone.0306117. eCollection 2024.

Abstract

The development of a cancer vaccine has become an essential focus in the field of medical biotechnology and immunology. In our study, the NY-SAR-35 cancer/testis antigen was targeted to design a novel peptide vaccine using bioinformatics tools, and BALB/c mice were used to evaluate the vaccine's immunological function. This evaluation involved assessing peptide-specific IgG levels in the serum via ELISA and measuring the levels of IFN-γ, IL-4, and granzyme B in the supernatant of cultured splenocytes. The final vaccine construct consisted of two T lymphocyte epitopes linked by the AAY linker. This construct displayed high antigenicity, non-allergenicity, non-toxicity, stability, and ability to induce IFN-γ and IL-4. It showed stable dynamics with both human MHC-I and II molecules, as well as mouse MHC-II molecules, and revealed strong Van der Waals and electrostatic energies. Emulsifying our peptide vaccine in incomplete Freund's adjuvant resulted in a remarkable increase in the levels of IgG. The splenocytes of mice that received the combination of peptide and adjuvant displayed a noteworthy increase in IFN-γ, IL-4, and granzyme B secretion. Additionally, their lymphocytes exhibited higher proliferation rates compared to the control group. Our data demonstrated that our vaccine could stimulate a robust immune response, making it a promising candidate for cancer prevention. However, clinical trials are necessary to assess its efficacy in humans.

摘要

癌症疫苗的开发已成为医学生物技术和免疫学领域的一个重要焦点。在我们的研究中,我们利用生物信息学工具针对 NY-SAR-35 癌症/睾丸抗原进行设计,构建了一种新型的肽疫苗,并使用 BALB/c 小鼠评估了该疫苗的免疫功能。我们通过 ELISA 检测血清中肽特异性 IgG 水平,通过培养脾细胞上清液中 IFN-γ、IL-4 和颗粒酶 B 的水平来评估疫苗的免疫功能。最终的疫苗构建体由两个 T 淋巴细胞表位通过 AAY 接头连接而成。该构建体具有高抗原性、无变应原性、无毒性、稳定性以及诱导 IFN-γ 和 IL-4 的能力。它与人类 MHC-I 和 II 分子以及小鼠 MHC-II 分子具有稳定的动力学,显示出较强的范德华力和静电力。在不完全弗氏佐剂中乳化我们的肽疫苗可显著提高 IgG 水平。接受肽和佐剂联合治疗的小鼠脾细胞 IFN-γ、IL-4 和颗粒酶 B 的分泌显著增加。此外,它们的淋巴细胞与对照组相比具有更高的增殖率。我们的数据表明,我们的疫苗可以刺激强烈的免疫反应,使其成为预防癌症的有前途的候选物。然而,需要进行临床试验来评估其在人类中的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d1/11207152/49599724a3c3/pone.0306117.g001.jpg

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