4.7 Article

Sendai Virus Mucosal Vaccination Establishes Lung-Resident Memory CD8 T Cell Immunity and Boosts BCG-Primed Protection against TB in Mice

期刊

MOLECULAR THERAPY
卷 25, 期 5, 页码 1222-1233

出版社

CELL PRESS
DOI: 10.1016/j.ymthe.2017.02.018

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资金

  1. Chinese National Mega Science and Technology Program on Infectious Diseases [2013ZX10003007-003]
  2. National Natural Science Foundation of China [81273328, 81501365]
  3. Shanghai Science and Technology Commission [17ZR1423900, 15ZR1434600]

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Accumulating evidence has shown the protective role of CD8(+) T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8(+) T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigens-pecific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice. Depletion of CD8(+) T cells abrogated the protective immunity afforded by SeV85AB vaccination. Interestingly, only SeV85AB vaccination induced high levels of lung-resident memory CD8(+) T (TRM) cells, and this led to a rapid and strong recall of antigen- specific CD8(+) T cell responses against Mtb challenge infection. Furthermore, when used in a BCG prime-SeV85AB boost strategy, SeV85AB vaccine significantly enhanced protection above that seen after BCG vaccination alone. Our findings suggest that CD8(+) TRM cells that arise in lungs responding to this mucosal vaccination might help to protect against TB, and SeV85AB holds notable promise to improve BCG's protective efficacy in a prime-boost immunization regimen.

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