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用微囊化的斯特恩34F2菌株芽孢进行口服疫苗接种后的保护性抗体反应。

Protective antibody response following oral vaccination with microencapsulated Sterne strain 34F2 spores.

作者信息

Benn Felix Jamie, Chaki Sankar P, Xu Yi, Ficht Thomas A, Rice-Ficht Allison C, Cook Walter E

机构信息

Texas A&M University, Department of Veterinary Pathobiology, College Station, TX 77843 USA.

Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030 USA.

出版信息

NPJ Vaccines. 2020 Jul 10;5:59. doi: 10.1038/s41541-020-0208-3. eCollection 2020.

Abstract

An oral vaccine against anthrax () is urgently needed to prevent annual anthrax outbreaks that are causing catastrophic losses in free-ranging livestock and wildlife worldwide. The Sterne vaccine, the current injectable livestock vaccine, is a suspension of live attenuated Sterne strain 34F2 spores (Sterne spores) in saponin. It is not effective when administered orally and individual subcutaneous injections are not a practical method of vaccination for wildlife. In this study, we report the development of a microencapsulated oral vaccine against anthrax. Evaluating Sterne spore stability at varying pH's in vitro revealed that spore exposure to pH 2 results in spore death, confirming that protection from the gastric environment is of main concern when producing an oral vaccine. Therefore, Sterne spores were encapsulated in alginate and coated with a protein shell containing poly-L-lysine (PLL) and vitelline protein B (VpB), a non-immunogenic, proteolysis resistant protein isolated from . Capsule exposure to pH 2 demonstrated enhanced acid gel character suggesting that alginate microcapsules provided the necessary protection for spores to survive the gastric environment. Post vaccination IgG levels in BALBc/J mouse serum samples indicated that encapsulated spores induced anti-anthrax specific responses in both the subcutaneous and the oral vaccination groups. Furthermore, the antibody responses from both vaccination routes were protective against anthrax lethal toxin in vitro, suggesting that further optimization of this vaccine formulation may result in a reliable oral vaccine that will conveniently and effectively prevent anthrax in wildlife populations.

摘要

迫切需要一种抗炭疽的口服疫苗,以预防每年在全球范围内自由放养的牲畜和野生动物中引发灾难性损失的炭疽疫情。目前的注射用牲畜疫苗——斯terne疫苗,是减毒活斯terne菌株34F2孢子(斯terne孢子)在皂苷中的悬浮液。口服时无效,而且对野生动物进行个体皮下注射并非切实可行的疫苗接种方法。在本研究中,我们报告了一种抗炭疽微囊化口服疫苗的研发情况。在体外评估斯terne孢子在不同pH值下的稳定性发现,孢子暴露于pH 2会导致孢子死亡,这证实了在生产口服疫苗时,保护孢子免受胃部环境影响是主要关注点。因此,将斯terne孢子包裹在藻酸盐中,并用含有聚-L-赖氨酸(PLL)和卵黄蛋白B(VpB)的蛋白壳包被,VpB是一种从[未提及具体来源]分离出的无免疫原性、抗蛋白水解的蛋白质。将胶囊暴露于pH 2显示出增强的酸性凝胶特性,表明藻酸盐微囊为孢子在胃部环境中存活提供了必要的保护。接种疫苗后BALBc/J小鼠血清样本中的IgG水平表明,包囊化的孢子在皮下和口服接种组中均诱导了抗炭疽特异性反应。此外,两种接种途径产生的抗体反应在体外对炭疽致死毒素具有保护作用,这表明进一步优化这种疫苗配方可能会产生一种可靠的口服疫苗,能够方便有效地预防野生动物群体中的炭疽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f1/7351773/c850d040178b/41541_2020_208_Fig1_HTML.jpg

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