Recombinant ArgF PLGA nanoparticles enhances BCG induced immune responses against Mycobacterium bovis infection

Biomed Pharmacother. 2021 May:137:111341. doi: 10.1016/j.biopha.2021.111341. Epub 2021 Feb 6.

Abstract

Mycobacterium bovis (M. bovis) is a member of mycobacterium tuberculosis complex (MTBC), and a causative agent of chronic respiratory disease in a wide range of hosts. Bacillus Calmette-Guerin (BCG) vaccine is mostly used for the prevention of childhood tuberculosis. Further substantial implications are required for the development and evaluation of new tuberculosis (TB) vaccines as well as improving the role of BCG in TB control strategies. In this study, we prepared PLGA nanoparticles encapsulated with argF antigen (argF-NPs). We hypothesized, that argF nanoparticles mediate immune responses of BCG vaccine in mice models of M. bovis infection. We observed that mice vaccinated with argF-NPs exhibited a significant increase in secretory IFN-γ, CD4+ T cells response and mucosal secretory IgA against M. bovis infection. In addition, a marked increase was observed in the level of secretory IL-1β, TNF-α and IL-10 both in vitro and in vivo upon argF-NPs vaccination. Furthermore, argF-NPs vaccination resulted in a significant reduction in the inflammatory lesions in the lung's tissues, minimized the losses in total body weight and reduced M. bovis burden in infected mice. Our results indicate that BCG prime-boost strategy might be a promising measure for the prevention against M. bovis infection by induction of CD4+ T cells responses and mucosal antibodies.

Keywords: ArgF; Immune responses; Mycobacterium bovis; PLGA nanoparticles; Targeted nanocarriers.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibody Formation / drug effects
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology*
  • Body Weight / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cattle
  • Cell Line
  • Disease Models, Animal
  • Female
  • Immunoglobulin A, Secretory / metabolism
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Lung / metabolism
  • Lung / microbiology
  • Lung / pathology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis* / growth & development
  • Mycobacterium bovis* / pathogenicity
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Ornithine Carbamoyltransferase / administration & dosage
  • Ornithine Carbamoyltransferase / chemistry
  • Ornithine Carbamoyltransferase / immunology*
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / immunology*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Spleen / microbiology
  • Spleen / pathology
  • Tuberculosis, Bovine / prevention & control*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • BCG Vaccine
  • IFNG protein, mouse
  • IL10 protein, mouse
  • IL1B protein, mouse
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Interleukin-1beta
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Interferon-gamma
  • Ornithine Carbamoyltransferase