Tao Pan, Mahalingam Marthandan, Zhu Jingen, Moayeri Mahtab, Kirtley Michelle L, Fitts Eric C, Andersson Jourdan A, Lawrence William S, Leppla Stephen H, Chopra Ashok K, Rao Venigalla B
Department of Biology, The Catholic University of America, Washington, DC, United States.
Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2017 Jun 26;8:687. doi: 10.3389/fimmu.2017.00687. eCollection 2017.
Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, and , the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from and PA from , in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against challenge with and the lethal toxin of , demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized and/or . This bivalent anthrax-plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats.
生物恐怖主义仍然是全球安全和公共卫生面临的最大挑战之一。自2001年美国发生致命的炭疽袭击事件以来，炭疽杆菌和鼠疫杆菌分别成为臭名昭著的病原体，并被美国疾病控制与预防中心列为一级生物威胁因子。目前，美国食品药品监督管理局尚未批准针对上述任何一种威胁的疫苗用于大规模接种以保护公众，更不用说二价疫苗了。在此，我们报告了一种单一重组疫苗的研发情况，该疫苗是一种三联抗原，由来自鼠疫杆菌的F1和V以及来自炭疽杆菌的保护性抗原（PA）这三种目标抗原在结构稳定的环境中组成。这种三联抗原正确折叠且可溶，保留了所有三种抗原的功能和免疫原性。值得注意的是，两剂这种与氢氧化铝佐剂联合使用的免疫原在小鼠、大鼠和兔子中引发了强烈的抗体反应，并对吸入性炭疽和肺鼠疫提供了完全保护。未观察到明显的抗原干扰。此外，我们首次报告了动物对鼠疫杆菌攻击以及炭疽杆菌致死毒素攻击具有完全保护作用，这表明一种单一的生物防御疫苗可以抵御用武器化的鼠疫杆菌和/或炭疽杆菌进行的生物恐怖袭击。因此，在人体临床试验中证明其安全性和免疫原性之后，这种二价炭疽 - 鼠疫疫苗作为国家防范两种最致命生物恐怖威胁的一部分，是储备的有力候选疫苗。
