ABSTRACT
Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Antigens, Bacterial/immunology , Cord Factors/administration & dosage , Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/immunology , Tuberculosis, Pulmonary/prevention & control , Vaccines, DNA/immunology , Animals , Antigens, Bacterial/genetics , Bacterial Load , Disease Models, Animal , Drug Carriers/administration & dosage , Female , Humans , Lung/microbiology , Lung/pathology , Mice , Mice, Inbred BALB C , Microspheres , Mycobacterium tuberculosis/genetics , Tuberculosis Vaccines/administration & dosage , Tuberculosis Vaccines/genetics , Tuberculosis, Pulmonary/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/geneticsABSTRACT
Helminths are known to elicit a wide range of immunomodulation characterized by dominant Th2-type immune responses. Our group previously showed that a DNA vaccine encoding the mycobacterial 65-kDa heat shock protein (DNA-hsp65) showed immunomodulatory properties. We also showed, using a helminth-tuberculosis (TB) co-infection model, that the DNA-hsp65 vaccine protected mice against TB. We next investigated the mechanistic role of the vaccine during helminth-TB co-infection. Clinically, helminth infection causes type 2 granulomas in the lung. Mice were immunized with DNA-hsp65 while they were submitted to the type 2 granuloma induction protocol by Schistosoma mansoni eggs infusion. In this work we investigated the effects of DNA-hsp65 on the pathology and immune response during the development of type 2 granuloma induced by S. mansoni eggs. Histologic analyses of lung parenchyma showed that the DNA-hsp65 vaccine protected mice against exacerbated fibrosis induced by Schistosoma eggs, and decreased the size of the granulomas. These changes were correlated with a reduction in the number of T cells specific for the egg antigens in the lung and also with modulation of Th2 cytokine expression. Taken together, our results showed that the adjuvant properties of the DNA-hsp65 vaccine regulated the immune response in this Th2 model, and resulted in a preserved lung parenchyma.
Subject(s)
Cell Movement , Cytokines/metabolism , Fibrosis/prevention & control , Granuloma/prevention & control , Myofibroblasts/pathology , Schistosomiasis mansoni/prevention & control , Vaccines, DNA/therapeutic use , Animals , Blotting, Western , Cell Proliferation , Female , Fibrosis/immunology , Fibrosis/metabolism , Fluorescent Antibody Technique , Granuloma/immunology , Granuloma/metabolism , Lung/immunology , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Myofibroblasts/immunology , Myofibroblasts/metabolism , Ovum/immunology , Ovum/metabolism , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Schistosoma mansoni/genetics , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Th2 Cells/immunology , Th2 Cells/metabolism , Th2 Cells/pathologyABSTRACT
Antibody Response from Whole-Cell Pertussis Vaccine Immunized Brazilian Children against Different Strains of Bordetella pertussisBordetella pertussis is a gram-negative bacillus that causes the highly contagious disease known as pertussis or whooping cough. Antibody response in children may vary depending on the vaccination schedule and the product used. In this study, we have analyzed the antibody response of cellular pertussis vaccinated children against B. pertussis strains and their virulence factors, such as pertussis toxin, pertactin, and filamentous hemagglutinin. After the completion of the immunization process, according to the Brazilian vaccination program, children serum samples were collected at different periods of time, and tested for the presence of specific antibodies and antigenic cross-reactivity. Results obtained show that children immunized with three doses of the Brazilian whole-cell pertussis vaccine present high levels of serum antibodies capable of recognizing the majority of the components present in vaccinal and non-vaccinal B. pertussis strains and their virulence factors for at least 2 years after the completion of the immunization procedure.
