Gupta Tuhina, LaGatta Monica, Helms Shelly, Pavlicek Rebecca L, Owino Simon O, Sakamoto Kaori, Nagy Tamas, Harvey Stephen B, Papania Mark, Ledden Stephanie, Schultz Kevin T, McCombs Candace, Quinn Frederick D, Karls Russell K
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA; Pathens, Inc., Athens, GA, USA.
Tuberculosis (Edinb). 2018 Dec;113:179-188. doi: 10.1016/j.tube.2018.10.006. Epub 2018 Oct 19.
Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.
结核病（TB）目前是由单一传染源结核分枝杆菌导致人类死亡的首要原因。卡介苗（BCG）疫苗预防肺结核的效果不一，但可在感染艾滋病毒的婴儿中引发危及生命的全身感染。在本研究中，对表达结核分枝杆菌抗原85B的肖氏分枝杆菌衍生物TBvac85作为卡介苗更安全的替代物进行了检测。用天然温度受限的TBvac85对豚鼠进行鼻内接种，可产生血清Ag85B特异性IgG抗体。基于结核分枝杆菌埃尔德曼菌株气溶胶攻击六周后的器官细菌负荷和肺部病理情况，通过该途径接种疫苗还诱导出了与皮内接种卡介苗相当的保护作用。这些结果支持了TBvac85作为有效结核病疫苗基础的潜力。表达多种结核分枝杆菌免疫原的下一代衍生物正在研发中。
