Humoral and Cellular Immune Response to the Genetically Detoxified S1 Subunit of Pertussis Toxin in Mice

IF 1.4 Q4 CELL BIOLOGY

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2025-06-13 DOI:10.1134/S1990747825700163

V. A. Shokina, A. V. Maleeva, V. P. Volok, O. V. Shcherbakova, N. E. Postika, A. V. Melikhova, D. Y. Mokhirev, A. A. Tikhonova, D. Engin, A. V. Lukina-Gronskaya, I. S. Rog, I. K. Chudinov, A. A. Lazareva, A. V. Kovalenko, Y. E. Kuzmina, O. V. Fedorov, A. S. Speranskaya, A. V. Kudriavtsev

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Abstract

Bordetella pertussis, a gram-negative bacterium responsible for whooping cough, poses severe health risks, especially to young children. However, the disease can be prevented by immunization with whole-cell pertussis vaccines and acellular pertussis vaccines containing 2–5 purified B. pertussis antigens, of which chemically detoxified pertussis toxin is the main protective component. While current vaccines have proven effective, concerns over high reactogenicity of whole-cell pertussis vaccines and the waning immunity to acellular pertussis vaccines formulations underscore the need for improved pertussis vaccines. Genetically detoxified pertussis toxin is an attractive vaccine candidate because it retains most of the structural properties of native pertussis toxin and better preserves the protective epitopes compared to detoxified pertussis toxin. In this study, we developed a candidate vaccine based on a genetically detoxified pertussis toxin S1 subunit, gd15PTxS1. We evaluated humoral and cellular immunogenicity of gd15PTxS1 in a murine model and demonstrated significant anti-PTx IgG seroconversion and a balanced Th1/Th2/Th17 T-cell response, with gd15PTxS1 inducing robust cytotoxic and helper T-cell activation comparable to that of the whole-cell pertussis vaccines. Our results show that gd15PTxS1 is highly immunogenic in mice and is a promising vaccine candidate for further protectivity studies.

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小鼠对百日咳毒素基因解毒S1亚基的体液和细胞免疫反应

百日咳博德泰拉是一种导致百日咳的革兰氏阴性细菌，对健康构成严重威胁，尤其是对幼儿。但是，可以通过免疫全细胞百日咳疫苗和含有2-5种纯化百日咳抗原的无细胞百日咳疫苗来预防该病，其中化学解毒百日咳毒素是主要的保护成分。虽然目前的疫苗已被证明是有效的，但对全细胞百日咳疫苗的高反应原性和对非细胞百日咳疫苗配方的免疫力下降的担忧强调了改进百日咳疫苗的必要性。遗传解毒百日咳毒素是一种有吸引力的候选疫苗，因为它保留了天然百日咳毒素的大部分结构特性，并且与解毒百日咳毒素相比，它更好地保留了保护性抗原表位。在这项研究中，我们开发了一种基于基因解毒百日咳毒素S1亚基gd15PTxS1的候选疫苗。我们在小鼠模型中评估了gd15PTxS1的体液和细胞免疫原性，并证明了显著的抗ptx IgG血清转化和平衡的Th1/Th2/Th17 t细胞反应，gd15PTxS1诱导了与全细胞百日咳疫苗相当的强大的细胞毒性和辅助性t细胞激活。我们的研究结果表明，gd15PTxS1在小鼠中具有高度的免疫原性，是一种有希望进行进一步保护性研究的候选疫苗。

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来源期刊

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology CELL BIOLOGY-

CiteScore

1.40

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.