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-1ß, 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.
Subject(s)
BCG Vaccine/administration & dosage , BCG Vaccine/immunology , Mycobacterium bovis , Nanoparticles/administration & dosage , Ornithine Carbamoyltransferase/immunology , Polylactic Acid-Polyglycolic Acid Copolymer/immunology , Tuberculosis, Bovine/prevention & control , Administration, Intranasal , Animals , Antibody Formation/drug effects , 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, Inbred BALB C , Mycobacterium bovis/growth & development , Mycobacterium bovis/pathogenicity , Nanoparticles/chemistry , Ornithine Carbamoyltransferase/administration & dosage , Ornithine Carbamoyltransferase/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Spleen/microbiology , Spleen/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide, yet preventive medical strategies are not available. A crude veterinary vaccine has been licensed for cats and dogs, but no defined human vaccine is available. We tested the vaccine potential of three conserved antigens previously identified in human and murine giardiasis, α1-giardin, α-enolase, and ornithine carbamoyl transferase, in a murine model of G. lamblia infection. Live recombinant attenuated Salmonella enterica Serovar Typhimurium vaccine strains were constructed that stably expressed each antigen, maintained colonization capacity, and sustained total attenuation in the host. Oral administration of the vaccine strains induced antigen-specific serum IgG, particularly IgG(2A), and mucosal IgA for α1-giardin and α-enolase, but not for ornithine carbamoyl transferase. Immunization with the α1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual α1-giardin administration. The α-enolase vaccine afforded no protection. Analysis of α1-giardin from divergent assemblage A and B isolates of G. lamblia revealed >97% amino acid sequence conservation and immunological cross-reactivity, further supporting the potential utility of this antigen in vaccine development. Together. These results indicate that α1-giardin is a suitable candidate antigen for a vaccine against giardiasis.
