Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California - Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1688, USA.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.
Sci Rep. 2018 May 3;8(1):7009. doi: 10.1038/s41598-018-24581-y.
Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of Tier 1 Select Agents anthrax, plague, and tularemia, respectively. Currently, there are no licensed vaccines against plague and tularemia and the licensed anthrax vaccine is suboptimal. Here we report F. tularensis LVS ΔcapB (Live Vaccine Strain with a deletion in capB)- and attenuated multi-deletional Listeria monocytogenes (Lm)-vectored vaccines against all three aforementioned pathogens. We show that LVS ΔcapB- and Lm-vectored vaccines express recombinant B. anthracis, Y. pestis, and F. tularensis immunoprotective antigens in broth and in macrophage-like cells and are non-toxic in mice. Homologous priming-boosting with the LVS ΔcapB-vectored vaccines induces potent antigen-specific humoral and T-cell-mediated immune responses and potent protective immunity against lethal respiratory challenge with all three pathogens. Protection against anthrax was far superior to that obtained with the licensed AVA vaccine and protection against tularemia was comparable to or greater than that obtained with the toxic and unlicensed LVS vaccine. Heterologous priming-boosting with LVS ΔcapB- and Lm-vectored B. anthracis and Y. pestis vaccines also induced potent protective immunity against lethal respiratory challenge with B. anthracis and Y. pestis. The single vaccine platform, especially the LVS ΔcapB-vectored vaccine platform, can be extended readily to other pathogens.
炭疽芽孢杆菌、鼠疫耶尔森菌和土拉弗朗西斯菌分别是 1 级选择剂炭疽、鼠疫和土拉热的病原体。目前，尚无针对鼠疫和土拉热的许可疫苗，而许可的炭疽疫苗也不尽如人意。在这里，我们报告了 F. tularensis LVS ΔcapB（capB 缺失的活疫苗株）和减毒多缺失李斯特菌（Lm）载体疫苗，可预防上述三种病原体。我们表明，LVS ΔcapB 和 Lm 载体疫苗在肉汤和巨噬细胞样细胞中表达重组 B. anthracis、Y. pestis 和 F. tularensis 免疫保护性抗原，且在小鼠中无毒性。同源初免-加强免疫 LVS ΔcapB 载体疫苗可诱导针对三种病原体的强效抗原特异性体液和细胞介导的免疫应答，并产生针对三种病原体致死性呼吸道攻击的有效保护。炭疽的保护作用远优于许可的 AVA 疫苗，而土拉热的保护作用与毒性和未许可的 LVS 疫苗相当或更高。用 LVS ΔcapB 和 Lm 载体疫苗进行异源初免-加强免疫也可诱导针对炭疽和鼠疫的致死性呼吸道攻击的有效保护。单一疫苗平台，尤其是 LVS ΔcapB 载体疫苗平台，可轻松扩展到其他病原体。
