TY - JOUR
T1 - A novel nanoemulsion vaccine induces mucosal Interleukin-17 responses and confers protection upon Mycobacterium tuberculosis challenge in mice
AU - Ahmed, Mushtaq
AU - Smith, Douglas M.
AU - Hamouda, Tarek
AU - Rangel-Moreno, Javier
AU - Fattom, Ali
AU - Khader, Shabaana A.
N1 - Funding Information:
This work was supported by Washington University in St Louis, National Institutes of Health grants HL105427 and AI127172 to S.A.K. J.R.-M. was supported by funds of the Department of Medicine, University of Rochester . The authors thank Sarah Squires (WashU) for animal breeding. The authors have no conflicts to report.
Funding Information:
This work was supported by Washington University in St Louis, National Institutes of Health grants HL105427 and AI127172 to S.A.K. J.R.-M. was supported by funds of the Department of Medicine, University of Rochester. The authors thank Sarah Squires (WashU) for animal breeding. The authors have no conflicts to report.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/9/5
Y1 - 2017/9/5
N2 - 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.
AB - 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.
KW - IL-17 Responses
KW - Mucosal vaccines
KW - Nanoemulsion
UR - http://www.scopus.com/inward/record.url?scp=85026360942&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2017.07.073
DO - 10.1016/j.vaccine.2017.07.073
M3 - Article
C2 - 28774560
AN - SCOPUS:85026360942
SN - 0264-410X
VL - 35
SP - 4983
EP - 4989
JO - Vaccine
JF - Vaccine
IS - 37
ER -