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减毒蝎毒素诱导的长期抗体应答和保护作用:记忆浆细胞的参与。

Long-term antibody response and protective effect induced by attenuated scorpion toxins: Involvement of memory plasma cells.

机构信息

USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP 32 El-Alia, Bab Ezzouar, Algiers, Algeria.

USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP 32 El-Alia, Bab Ezzouar, Algiers, Algeria.

出版信息

Immunobiology. 2021 Jul;226(4):152108. doi: 10.1016/j.imbio.2021.152108. Epub 2021 Jul 2.

DOI:10.1016/j.imbio.2021.152108
PMID:34247017
Abstract

In Algeria, Androctonus australis hector scorpion envenomation remains a major problem of public health because of non-efficient therapy. The development of safe vaccine against scorpion venom could be one key strategy for the envenomation prevention. The irradiation of venom by γ-rays develops suitable immunogens which produced effective antivenom and safe vaccine. In this study, we investigated the ability of the irradiated toxic fraction (γ-FtoxG50) to induce long-term memory humoral response in immunized animals (mice and rabbits), by involving the long-lived plasma cells to prevent efficiently the lethality of scorpion envenomation. For this purpose, an appropriate immunization schedule was established in mice and rabbits using three (3) similar doses of γ-FtoxG50 associated with Alum adjuvant. Obtained results indicate that the long-term immunogenicity of γ-FtoxG50 is able to induce the long-term memory humoral response with a high level of specific antibodies. The long-term persistence of antibody levels could depend on bone marrow memory plasma cells. These cells produce continuously antibodies without antigen stimulus. Furthermore, an enhanced memory response was obtained post-repeated envenomation with toxic native venom that leads to improved protection of animals. Together, pre-existing protective antibodies and the activation of memory B-cells could induce a rapid neutralization of scorpion toxins and long-term protection against scorpion envenomation.

摘要

在阿尔及利亚,由于治疗效果不佳,安德罗克图斯澳大利亚海克托毒蝎螫伤仍然是一个主要的公共卫生问题。开发针对蝎毒的安全疫苗可能是预防螫伤的关键策略之一。γ 射线辐照毒液可产生合适的免疫原,从而产生有效的抗毒液和安全疫苗。在这项研究中,我们通过涉及长寿浆细胞来研究辐照的毒性部分(γ-FtoxG50)在免疫动物(小鼠和兔子)中诱导长期记忆体液反应的能力,以有效预防蝎毒中毒的致死性。为此,我们在小鼠和兔子中使用三种(3)类似剂量的γ-FtoxG50 联合 Alum 佐剂建立了适当的免疫方案。结果表明,γ-FtoxG50 的长期免疫原性能够诱导高水平特异性抗体的长期记忆体液反应。抗体水平的长期持续存在可能依赖于骨髓记忆浆细胞。这些细胞在没有抗原刺激的情况下持续产生抗体。此外,在重复用毒性天然毒液螫伤后获得了增强的记忆反应,从而提高了对动物的保护作用。总之,预先存在的保护性抗体和记忆 B 细胞的激活可以诱导蝎毒素的快速中和,并长期预防蝎毒中毒。

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