Abstract
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 LIΔactAplcB-Rv3875 (Δ refers to gene deletion in the bacterial genome) or LIΔactAplcB-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.
Highlights
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
C57BL/6 J mice were inoculated with 108 CFU of LIΔ-Rv3875 or LIΔ-Rv0129c, and the bacterial load in the liver, spleen and lung was detected at different days post inoculation
We reported the antigen-specific lung-localized cellular immune response and pulmonary mucosal secretory IgA (SIgA) antibody secretion after intranasal administration of LIΔ-Rv3875 or LIΔ-Rv0129c
Summary
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. Two recombinant attenuated LI strains expressing the ESAT-6 or Ag85C protein of Mtb were constructed, and an antigen-specific CD8+ T cell-mediated immune response was obtained via intravenous vaccination[17] Whether such recombinant strains could induce lung-localized and systemic cellular and humoral immune responses when intranasally administered to mice is still unknown. We evaluated the biosafety and immunogenicity of intranasal vaccination using two recombinant LI strains, LIΔactAplcB-Rv3875 (LIΔ-Rv3875) and LIΔactAplcB-Rv0129c (LIΔ-Rv0129c)[17], to verify our hypothesis We found that both strains induced lung-localized immune responses, including antigen-specific cellular immune responses and the secretion of secretory IgA (SIgA). Our research suggests that LI might be a novel and optimal live vector for respiratory mucosa vaccines
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