Goats Primed with Mycobacterium bovis BCG and Boosted with a Recombinant Adenovirus Expressing Ag85A Show Enhanced Protection against Tuberculosis
| Autor: | Mahavir Singh, Zhou Xing, Bernardo Villarreal-Ramos, Nadine Romera, H. Martin Vordermeier, Sergio López-Soria, Miquel Nofrarías, F. Xavier Abad, Bernat Pérez de Val, Mariano Domingo |
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| Rok vydání: | 2012 |
| Předmět: |
Microbiology (medical)
Tuberculosis Genetic Vectors Clinical Biochemistry Immunology Adenoviridae Interferon-gamma medicine Animals Immunology and Allergy Interferon gamma Tuberculosis Vaccines Lung Antigens Bacterial Drug Carriers Vaccines Synthetic Vaccines Mycobacterium bovis biology Goats Vaccination biology.organism_classification Mycobacterium caprae Vaccine efficacy medicine.disease Antibodies Bacterial Virology Disease Models Animal Humoral immunity Leukocytes Mononuclear Female Lymph Nodes Tuberculosis vaccines Acyltransferases medicine.drug |
| Zdroj: | Clinical and Vaccine Immunology. 19:1339-1347 |
| ISSN: | 1556-679X 1556-6811 |
| DOI: | 10.1128/cvi.00275-12 |
| Popis: | This is the first efficacy study using the experimental goat model, a natural host of tuberculosis (TB), to evaluate the efficacy of heterologousMycobacterium bovisbacillus Calmette-Guérin (BCG) prime followed by boosting with a replication-deficient adenovirus expressing the antigen Ag85A (AdAg85A). Three experimental groups of 11 goat kids each were used: BCG vaccinated, BCG vaccinated and AdAg85A boosted, and nonvaccinated. Twenty-two goat kids were vaccinated with ∼5 × 105CFU of BCG (week 0), and 11 of them were boosted at week 8 with 109PFU of AdAg85A. At week 14, all goats were challenged by the endobronchial route with ∼1.5 × 103CFU ofMycobacterium caprae. The animals were euthanized at week 28. Cellular and humoral immunity induced by vaccination andM. capraeinfection was measured throughout the study. After challenge BCG-AdAg85A-vaccinated animals exhibited reduced pathology compared to BCG-vaccinated animals in lungs and in pulmonary lymph nodes. There were significant reductions in bacterial load in both groups of vaccinated goats, but the reduction was more pronounced in prime-boosted animals. Antigen-specific gamma interferon (IFN-γ) and humoral responses were identified as prognostic biomarkers of vaccination outcome depending on their correlation with pathological and bacteriological results. As far as we know, this is the first report using multidetector computed tomography (MDCT) to measure vaccine efficacy against pulmonary TB in an animal model. The use in vaccine trials of animals that are natural hosts of TB may improve research into human TB vaccines. |
| Databáze: | OpenAIRE |
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