Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5536986 | Vaccine | 2017 | 7 Pages |
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-17Â 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.
Keywords
Ag85BTLRMPLchemokine (C-X-C motif) ligand 2MTBIFNγchemokine (C-X-C motif) ligand 9CCL-5Th1s.cESAT-6Th17μgMicrogramT helper type 17Antigen 85BMVA85ATGF-βT helper type 1centigradeMycobacterium bovis Bacillus Calmette-GuérinBCGMYD88CFUDAPIμLμMPBS4',6-diamidino-2-phenylindoleBCIP/NBTC57BL/6JHLTS.D.Heat labile enterotoxinstandard deviationinterleukinIntranasalTuberculosisTransforming Growth Factor Betaanalysis of varianceANOVAToll-like receptorcluster of differentiationsubcutaneousDendritic cellsPhosphate buffered salineMonophosphoryl lipid AMycobacterium tuberculosisnot significantmilliliterMicrolitermicrometerNanoemulsionnanometerMucosal vaccinesmyeloid differentiation primary response gene 88colony forming uniti.n.chemokine (C-C motif) ligand 5Interferon gamma
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Authors
Mushtaq Ahmed, Douglas M. Smith, Tarek Hamouda, Javier Rangel-Moreno, Ali Fattom, Shabaana A. Khader,