title: A multi-antigenic adenoviral-vectored vaccine improves BCG-induced protection of goats against pulmonary tuberculosis infection and prevents disease progression.
abstract: The "One world, one health" initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions. Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG.
authors.affiliation: Centre de Recerca en Sanitat Animal, Universitat autonoma de Barcelona-Investigación y tecnología Agroalimentarias, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Pérez de Val
authors.forename: Enric
authors.initials: E
authors.lastname: Vidal
authors.forename: Bernardo
authors.initials: B
authors.lastname: Villarreal-Ramos
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Anna
authors.initials: A
authors.lastname: Andaluz
authors.forename: Xavier
authors.initials: X
authors.lastname: Moll
authors.forename: Maite
authors.initials: M
authors.lastname: Martín
authors.forename: Miquel
authors.initials: M
authors.lastname: Nofrarías
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: Mariano
authors.initials: M
authors.lastname: Domingo
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000820:Animal Diseases / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D058491:Bacterial Load; D001835:Body Weight; D018450:Disease Progression; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D006041:Goats; D006099:Granuloma / Q000473:pathology; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000662:veterinary*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007371:Interferon-gamma