Department of Veterinary Pathology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, 24341, Republic of Korea.
Infectious Disease Research Center (Superbacteria Group), Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
BMC Vet Res. 2020 Jul 28;16(1):259. doi: 10.1186/s12917-020-02468-3.
Bacillus anthracis is the causative agent of anthrax, a disease of both humans and various animal species, and can be used as a bioterror agent. Effective vaccines are available, but those could benefit from improvements, including increasing the immunity duration, reducing the shot frequency and adverse reactions. In addition, more sophisticated antigen delivery and potentiation systems are urgently required. The protective antigen (PA), one of three major virulence factors associated with anthrax was displayed on the surface of Bacillus subtilis spores, which is a vaccine production host and delivery vector with several advantages such as a low production cost, straightforward administration as it is safe for human consumption and the particulate adjuvanticity. Mice were immunized orally (PO), intranasally (IN), sublingually (SL) or intraperitoneally (IP) with the PA displaying probiotic spore vaccine. Clinical observation, serological analysis and challenge experiment were conducted to investigate the safety and efficacy of the vaccine.
A/J mice immunized with the PA spore vaccine via PO, IN, SL, and IP were observed to have increased levels of active antibody titer, isotype profiles and toxin neutralizing antibody in sera, and IgA in saliva. The immunized mice were demonstrated to raise protective immunity against the challenge with lethal B. anthracis spores.
In this study, we developed a B. subtilis spore vaccine that displays the PA on its surface and showed that the PA-displaying spore vaccine was able to confer active immunity to a murine model based on the results of antibody isotype titration, mucosal antibody identification, and a lethal challenge experiment.
炭疽芽孢杆菌是炭疽病的病原体，炭疽病是一种人类和各种动物物种都会患的疾病，并且可以用作生物恐怖剂。目前已有有效的疫苗，但这些疫苗可以受益于改进，包括提高免疫持续时间、减少注射频率和不良反应。此外，还迫切需要更复杂的抗原传递和增强系统。保护性抗原（PA）是与炭疽相关的三个主要毒力因子之一，它被展示在枯草芽孢杆菌孢子的表面，枯草芽孢杆菌是一种疫苗生产宿主和递送载体，具有几个优点，如生产成本低、作为人类食用的安全药物，直接给药，以及颗粒状佐剂性。通过口服（PO）、鼻腔内（IN）、舌下（SL）或腹腔内（IP）免疫 PA 展示益生菌孢子疫苗，对小鼠进行了临床观察、血清学分析和攻毒实验，以研究疫苗的安全性和有效性。
通过 PO、IN、SL 和 IP 用 PA 孢子疫苗免疫的 A/J 小鼠，其血清中的活性抗体滴度、同种型谱和毒素中和抗体以及唾液中的 IgA 水平均升高。免疫小鼠对致死性炭疽芽孢杆菌孢子的攻击表现出保护免疫力。
在这项研究中，我们开发了一种枯草芽孢杆菌孢子疫苗，该疫苗在其表面展示 PA，并通过抗体同种型滴度测定、粘膜抗体鉴定和致死性攻毒实验表明，PA 展示孢子疫苗能够为小鼠模型提供主动免疫。
