title: Goats primed with Mycobacterium bovis BCG and boosted with a recombinant adenovirus expressing Ag85A show enhanced protection against tuberculosis.
abstract: This is the first efficacy study using the experimental goat model, a natural host of tuberculosis (TB), to evaluate the efficacy of heterologous Mycobacterium bovis bacillus 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 × 10(5) CFU of BCG (week 0), and 11 of them were boosted at week 8 with 10(9) PFU of AdAg85A. At week 14, all goats were challenged by the endobronchial route with ∼1.5 × 10(3) CFU of Mycobacterium caprae. The animals were euthanized at week 28. Cellular and humoral immunity induced by vaccination and M. caprae infection 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.
authors: Centre de Recerca en Sanitat Animal, UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain.
authors: Bernat
authors: B
authors: Pérez de Val
authors: Bernardo
authors: B
authors: Villarreal-Ramos
authors: Miquel
authors: M
authors: Nofrarías
authors: Sergio
authors: S
authors: López-Soria
authors: Nadine
authors: N
authors: Romera
authors: Mahavir
authors: M
authors: Singh
authors: F Xavier
authors: FX
authors: Abad
authors: Zhou
authors: Z
authors: Xing
authors: H Martin
authors: HM
authors: Vordermeier
authors: Mariano
authors: M
authors: Domingo
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006041:Goats; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004337:Drug Carriers; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis