Ahmed Mushtaq, Smith Douglas M, Hamouda Tarek, Rangel-Moreno Javier, Fattom Ali, Khader Shabaana A
Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO 63110, United States.
NanoBio Corporation, Ann Arbor, MI 48105, United States.
Vaccine. 2017 Sep 5;35(37):4983-4989. doi: 10.1016/j.vaccine.2017.07.073. Epub 2017 Jul 31.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is contracted via aerosol infection, typically affecting the lungs. Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only licensed vaccine and has variable efficacy in protecting against pulmonary TB. Additionally, chemotherapy is associated with low compliance contributing to development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb. Thus, there is an urgent need for the design of more effective vaccines against TB. Experimental vaccines delivered through the mucosal route induce robust T helper type 17 (Th17)/ Interleukin (IL) -17 responses and provide superior protection against Mtb infection. Thus, the development of safe mucosal adjuvants for human use is critical. In this study, we demonstrate that nanoemulsion (NE)-based adjuvants when delivered intranasally along with Mtb specific immunodominant antigens (NE-TB vaccine) induce potent mucosal IL-17T-cell responses. Additionally, the NE-TB vaccine confers significant protection against Mtb infection, and when delivered along with BCG, is associated with decreased disease severity. These findings strongly support the development of a NE-TB vaccine as a novel, safe and effective, first-of-kind IL-17 inducing mucosal vaccine for potential use in humans.
由结核分枝杆菌(Mtb)引起的结核病(TB)通过气溶胶感染传播,通常影响肺部。牛分枝杆菌卡介苗(BCG)是唯一获得许可的疫苗,在预防肺结核方面的效果不一。此外,化疗的依从性较低,导致了耐多药(MDR)和广泛耐药(XDR)结核分枝杆菌的产生。因此,迫切需要设计出更有效的抗结核疫苗。通过黏膜途径递送的实验性疫苗可诱导强大的17型辅助性T细胞(Th17)/白细胞介素(IL)-17反应,并为抵抗Mtb感染提供更好的保护。因此,开发用于人类的安全黏膜佐剂至关重要。在本研究中,我们证明基于纳米乳剂(NE)的佐剂与Mtb特异性免疫显性抗原一起经鼻递送(NE-TB疫苗)时,可诱导强大的黏膜IL-17 T细胞反应。此外,NE-TB疫苗对Mtb感染具有显著的保护作用,与卡介苗一起递送时,可降低疾病严重程度。这些发现有力地支持了开发NE-TB疫苗,作为一种新型、安全有效的、首创的诱导IL-17的黏膜疫苗,有可能用于人类。