Intranasal vaccination with Listeria ivanovii as vector of Mycobacterium tuberculosis antigens promotes specific lung-localized cellular and humoral immune responses

• Published in: Scientific reports 2020-01, Vol.10 (1), p.302-302, Article 302
• Main Authors: Jiang, Ming-juan, Liu, Si-jing, Su, Lin, Zhang, Xiang, Li, Yong-yu, Tang, Tian, Wang, Chuan
• Format: Article
• Language: English
• Subjects: 13/51; 631/250/347; 631/326/590; 96/21; 96/31; Administration, Intranasal; Ag85C protein; Alveoli; Animals; Antigens; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Bacterial Load; Bronchoalveolar Lavage Fluid - chemistry; Bronchus; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Clonal deletion; ESAT-6 antigen; Female; Gene deletion; Genomes; Humanities and Social Sciences; Immune response (cell-mediated); Immune response (humoral); Immunity, Cellular; Immunity, Humoral; Immunization; Immunoglobulin A; Immunoglobulin A - metabolism; Immunoglobulin G; Immunoglobulin G - blood; Inoculation; Interferon-gamma - metabolism; Intravenous administration; Listeria; Listeria - metabolism; Listeria - pathogenicity; Listeria ivanovii; Lung - immunology; Lung - metabolism; Lung - pathology; Lymphocytes T; Mice; Mice, Inbred C57BL; Mucosa; multidisciplinary; Mycobacterium tuberculosis; Respiratory diseases; Science; Science (multidisciplinary); Spleen; Strains (organisms); Tuberculosis; Tuberculosis Vaccines - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vaccination; Vaccines; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-57245-6

We have previously demonstrated that a recombinant Listeria ivanovii (LI) strain expressing the ESAT-6 or Ag85C protein of Mycobacterium tuberculosis (Mtb) as a tuberculosis (TB) vaccine candidates induced antigen-specific cellular immune responses after intravenous immunization of mice. However, whether such recombinant strains could induce desired immune responses in the lung, where TB infection occurs, is not clear. In this paper, C57BL/6 J mice were intranasally vaccinated with attenuated LI ΔactAplcB - Rv3875 ( Δ refers to gene deletion in the bacterial genome) or LI ΔactAplcB - Rv0129c , the two vaccine candidates that utilize LI as an antigen delivery vector. Bacterial load in the target organs, histological changes in the infected organs, the percentage of specific cytokine-secreting T cells in the lung and spleen, IgG levels in the serum and secretory IgA (SIgA) levles in bronchoalveolar lavage (BAL) fluid were determined at specific days post inoculation (dpi). The results showed that both strains were mainly confined to the lung and were eliminated at 10 dpi. The histological damage caused by the infection in the lung was slight and recovered by day 5. Intranasal vaccination of the mice twice at an interval of 4 weeks notably elicited TB antigen-specific CD4 + and CD8 + T cell responses in the lung and SIgA secretion in the pulmonary mucosa, and significantly enhanced the percentage of double-functional CD8 + T cells (IFN-γ + TNF-α + CD8 + ). To our knowledge, this is the first report regarding the used of LI vector vaccines to induce promising lung-localized cellular and humoral immune responses by intranasal vaccination. These data suggest that LI could be a novel and promising live vector to construct an intranasal vaccine against respiratory diseases.