Preclinical Progress of Subunit and Live AttenuatedMycobacterium tuberculosisVaccines: A Review following the First in Human Efficacy Trial
PHARMACEUTICS
Authors: Watt, Jacqueline; Liu, Jun
Abstract
Tuberculosis (TB) is the global leading cause of death from an infectious agent with approximately 10 million new cases of TB and 1.45 million deaths in 2018. Bacille Calmette-Guerin (BCG) remains the only approved vaccine forMycobacterium tuberculosis(M. tb, causative agent of TB), however clinical studies have shown BCG has variable effectiveness ranging from 0-80% in adults. With 1.7 billion people latently infected, it is becoming clear that vaccine regimens aimed at both post-exposure and pre-exposure toM. tbwill be crucial to end the TB epidemic. The two main strategies to improve or replace BCG are subunit and live attenuated vaccines. However, following the failure of the MVA85A phase IIb trial in 2013, more varied and innovative approaches are being developed. These include recombinant BCG strains, genetically attenuatedM. tband naturally attenuated mycobacteria strains, novel methods of immunogenic antigen discovery including for hypervirulentM. tbstrains, improved antigen recognition and delivery strategies, and broader selection of viral vectors. This article reviews preclinical vaccine work in the last 5 years with focus on those tested againstM. tbchallenge in relevant animal models.
Spoligotype Diversity of Mycobacterium tuberculosis over Two Decades from Tiruvallur, South India
INTERNATIONAL JOURNAL OF MICROBIOLOGY
Authors: Kumar, S. Siva; Kumar, S. Ashok; Sekar, Gomathi; Devika, K.; Bhasker, M.; Sriram, S.; Dolla, C. K.; Menon, Pradeep Aravindan; Tripathy, Srikanth Prasad; Narayanan, P. R.; Ranganathan, Uma Devi; Narayanan, Sujatha; Mondal, Rajesh
Abstract
Geographically, most tuberculosis (TB) cases in 2018 were reported from India. This TB burden is compounded by MDR-TB and XDR-TB. The strategies for the management and control of TB in the community depend on an understanding of the mode of spread of the different strains of TB isolates in the community. To determine the distribution and trends of M. tb strains over the time period in the community due to treatment, we carried out the present study on changes over two decades. Design/Methods. A total of 1218 M. tb isolates (year: 2001-2018) from Tiruvallur, India, were genotyped by spoligotyping after DNA extraction and subjected to anti-TB drug susceptibility testing for the first-line anti-TB drugs. Results. On analysis with the SpolDB4 database, majority (2001-2003: 53.32% and 2015-2018: 46.3%) of the isolates belonged to East African Indian (EAI) lineage, and the orphans designated in comparison to SpolDB4 stood 33% among 2001-2003 strain collection and 46.3% among 2015-2018 strain collection. 10.2% (2001-2003) and 9.26% (2015 to 2018) of isolates were monoresistant to isoniazid (H). MDR strains were less common among EAI strains (3.2%) compared to non-EAI strains (10.32%). Conclusions. EAI is the most predominant lineage in Tiruvallur, despite the presence of highly transmissible lineages like Beijing for the last two decades. The prevalence of MDR-TB is below the national average of 2-3% among the new TB cases in the last two decades. The reason can be attributed to the well-established nature of the locally circulating strains in this region which are not associated with drug resistance.