A novel nanoemulsion vaccine induces mucosal Interleukin-17 responses and confers protection upon Mycobacterium tuberculosis challenge in mice |
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| Affiliation: | 1. Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO 63110, United States;2. NanoBio Corporation, Ann Arbor, MI 48105, United States;3. Department of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY 14624, United States;1. Université de Bretagne Sud, UBS – Institut Dupuy de Lôme, Centre de Recherche, Rue de Saint Maudé, BP92116, 56321 Lorient Cedex, France;2. Department of Mechanical Engineering, Texas A&M University, Forsyth Chair in Mechanical Engineering, TX 77843, USA;1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;2. Faculty of Pharmacy, Shahid Sadoqi University of Medical Science, Yazd, Iran;1. Department of Molecular & Cellular Biochemistry, and Center for Structural Biology, University of Kentucky, Lexington, KY, 40536, United States;2. Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;3. Laboratory of Physics of Living Matter, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;1. Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy;2. Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France |
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| Abstract: | 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-17 T-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. |
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