A novel nanoemulsion vaccine induces mucosal Interleukin-17 responses and confers protection upon Mycobacterium tuberculosis challenge in mice

Vaccine. 2017 Sep 5;35(37):4983-4989. doi: 10.1016/j.vaccine.2017.07.073. Epub 2017 Jul 31.

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-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.

Keywords: IL-17 Responses; Mucosal vaccines; Nanoemulsion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigens, Bacterial / immunology
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity*
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis Vaccines / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Interleukin-17
  • Tuberculosis Vaccines