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

Mol Ther. 2017 May 3;25(5):1222-1233. doi: 10.1016/j.ymthe.2017.02.018. Epub 2017 Mar 23.

Abstract

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 antigen-specific 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.

Keywords: CD8(+) T cell responses; Mycobacterium tuberculosis; Sendai virus; TB vaccine; mucosal immunity; prime boost; resident memory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • BCG Vaccine / administration & dosage*
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Genetic Engineering
  • Immunity, Mucosal
  • Immunization, Secondary / methods*
  • Immunogenicity, Vaccine
  • Immunologic Memory
  • Lung / immunology
  • Lung / microbiology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / microbiology
  • Sendai virus / genetics*
  • Sendai virus / immunology
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccination / methods*

Substances

  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis
  • antigen 85B, Mycobacterium tuberculosis