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BA3338,一种具有表面层同源结构域的蛋白,增强了保护性抗原针对炭疽芽孢杆菌的免疫反应和保护效力,在小鼠模型中。

BA3338, a surface layer homology domain possessing protein augments immune response and protection efficacy of protective antigen against Bacillus anthracis in mouse model.

机构信息

Bioprocess Technology Division, Defence Research and Development Establishment, Gwalior, India.

出版信息

J Appl Microbiol. 2020 Aug;129(2):443-452. doi: 10.1111/jam.14624. Epub 2020 Mar 18.

DOI:10.1111/jam.14624
PMID:32118336
Abstract

AIM

Category A classified Bacillus anthracis is highly fatal pathogen that causes anthrax and creates challenges for global security and public health. In this study, development of a safe and ideal next-generation subunit anthrax vaccine has been evaluated in mouse model.

METHOD AND RESULTS

Protective antigen (PA) and BA3338, a surface layer homology (SLH) domain possessing protein were cloned, expressed in heterologous system and purified by IMAC. Recombinant PA and BA3338 with alum were administered in mouse alone or in combination. The humoral and cell-mediated immune response was measured by ELISA and vaccinated animals were challenged with B. anthracis spores via intraperitoneal route. The circulating IgG antibody titre of anti-PA and anti-BA3338 was found significantly high in the first and second booster sera. A significant enhanced level of IL-4, IFN-γ and IL-12 was observed in antigens stimulated supernatant of splenocytes of PA + BA3338 vaccinated animals. A combination of PA and BA3338 provided 80% protection against 20 LD lethal dose of B. anthracis spores.

CONCLUSION

Both antigens induced admirable humoral and cellular immune response as well as protective efficacy against B. anthracis spores.

SIGNIFICANCE AND IMPACT OF THE STUDY

This study has been evaluated for the first time using BA3338 as a vaccine candidate alone or in combination with well-known anthrax vaccine candidate PA. The findings of this study demonstrated that BA3338 could be a co-vaccine candidate for development of dual subunit vaccine against anthrax.

摘要

目的

A 类炭疽杆菌是一种高致命病原体,可引起炭疽病,对全球安全和公共卫生构成挑战。在本研究中,在小鼠模型中评估了安全且理想的下一代亚单位炭疽疫苗的开发。

方法和结果

克隆了保护性抗原 (PA) 和 BA3338,这是一种具有表面层同源 (SLH) 结构域的蛋白质,并在异源系统中表达和通过 IMAC 纯化。单独或联合用铝佐剂给重组 PA 和 BA3338 。通过 ELISA 测量体液和细胞介导的免疫反应,并通过腹腔途径用 B. anthracis 孢子对接种动物进行攻击。抗-PA 和抗-BA3338 的循环 IgG 抗体滴度在第一次和第二次加强血清中显着升高。在 PA + BA3338 疫苗接种动物的脾细胞刺激上清液中观察到显著增强的 IL-4、IFN-γ 和 IL-12 水平。PA 和 BA3338 的组合提供了对 20LD 致死剂量 B. anthracis 孢子的 80%保护。

结论

两种抗原均诱导了令人钦佩的体液和细胞免疫反应以及对 B. anthracis 孢子的保护效力。

研究的意义和影响

这是首次使用 BA3338 作为候选疫苗单独或与著名的炭疽疫苗候选物 PA 联合进行评估。这项研究的结果表明,BA3338 可能是开发针对炭疽的双亚单位疫苗的候选共同疫苗。

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