SapM mutation to improve the BCG vaccine: genomic, transcriptomic and preclinical safety characterization

EMBO Molecular Medicine, 2011

Vaccine, 2006

MBio, 2016

Proceedings of the National Academy of Sciences, 2000

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette–Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis ( M. tb. ), the primary causative agent of TB. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, these differences were highly si...

Infection and Immunity, 2005

Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available vaccine against tuberculosis. Thus, while more-potent vaccines are needed to replace BCG, new vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of pulmonary tuberculosis, the “gold standard” for testing tuberculosis vaccines. In this paper, we describe a booster vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa protein, the major secreted protein of this pathogen. In the guinea pig model of pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa protein greatly in...

Infection and …, 2000

Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and ...

BMC Genomics

Background: Bacillus Calmette–Guérin (BCG) remains the only vaccine to prevent tuberculosis (TB) during childhood, with relatively low to no efficacy against pulmonary TB in adolescents and adults. BCG consists of close to 15 different substrains, where genetic variations among them might contribute to the variable protective efficacy afforded against pulmonary TB. We have shown that the vaccine candidate, BCGΔBCG1419c, which is based on BCG Pasteur, improved protection against chronic TB in murine models, as well as against pulmonary and extrapulmonary TB in guinea pigs. Here, to confirm deletion of the BCG1419c gene and to detect possible genetic variations occurring as a consequence of the spontaneous mutations that may arise during in vitro culture of mycobacteria, the genomes of BCG Pasteur ATCC 35734 and its isogenic derivative, BCGΔBCG1419c, were sequenced and subjected to a comparative analysis between them and against BCG Pasteur 1173P2. Results: The complete catalog of var...

Infection and Immunity, 2000

Vaccine, 2003

Mycobacterium bovis Bacille Calmette-Guérin (BCG) is one of the most widely used vaccines. Modern techniques in genome manipulation allow the construction of recombinant (r)-BCG strains that can be employed as highly immunogenic vaccines against tuberculosis (TB) with an enhanced safety profile. In addition, the development of novel procedures to cultivate BCG will allow the large-scale production of future BCG-based vaccines.

(ARCHAEO)ASTRONOMY AND DEATH Proceedings of the National Symposium, 2022

The question of the astronomical knowledge of the Dacian elites is increasingly the subject of research on Dacian civilisation. Although initially these subjects were regarded with reluctance by the Romanian academic community, the results of multidisciplinary investigations have revealed a series of mathematical notions and realities in the sacred, civil and military architecture of the Dacian Kingdom derived and reflected from astronomical constants. On closer inspection, these interdisciplinary approaches are complemented by some iconographic elements identified on the decorations of some pieces of weaponry belonging to the warrior caste. The ornamentation of weapons with cosmic symbols shows the importance of the celestial vault and astral concepts in the mentality of the period and especially in that of the elite warriors of the Dacian Kingdom.