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.

Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep

“…The efficacy of the parenterally administration of the BCG vaccine in the reduction of clinical signs (pyrexia and prevention of weight loss), gross lesions and the incidence of positive immunological tests in lambs in this study has been also demonstrated in previous studies in different wildlife (wild brushtail possums and badgers) and domestic (cattle and goat) species [6, 12, 14, 27]. The efficacies of different inactivated formulations have been tested with promising results in some cases.…”

Diagnostic pathology in microbial diseases of sheep or goats

“…Gross pulmonary lesions are characterised by the presence of granulomas of variable size, sometimes confluent, in various stages of development and, preferentially, located in the diaphragmatic lobes (Daniel et al, 2009;Pérez de val et al, 2013). Some nodules have a solid appearance, while others show the characteristic central caseous necrosis and encapsulation (Supplemantary material 17); at later stages, the necrotic areas may undergo mineralisation and fibrosis or liquefaction to cavity formation (open tuberculosis).…”

Effects of the fusion design and immunization route on the immunogenicity of Ag85A-Mtb32 in adenoviral vectored tuberculosis vaccine

“…10 These strategies were also applied to the construction of other genetic vector based TB vaccines. 11,12 However, the influence of codon optimization, fusion linker, and signal sequence on the immunogenicity of vaccines containing multiple TB antigens has not been fully determined.…”