Vaccines for TB: Lessons from the Past Translating into Future Potentials

Tye, Gee Jun; Lew, Min Han; Choong, Yee Siew; Lim, Theam Soon; Sarmiento, María E.; Acosta, Armando; Norazmi, Mohd Nor

doi:10.1155/2015/916780

Cited by 10 publications

(5 citation statements)

References 92 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The majority of candidate vaccines were focused on improving CMI either by engineering the present BCG vaccine or using mycobacterial antigens that elicited Th1 responses as boosters after BCG priming. Interestingly, the vaccine strategies that use the whole cell (such as M. indicus pranii ) has reached phase III of clinical trials ( Weiner and Kaufmann, 2014 ; Tye et al, 2015 ). The success of this may be owing to a balanced stimulation of both CMI and AMI wings rather than trying to bias the same toward CMI.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

Vemula

Ganji

Sivangala³

et al. 2016

Front. Microbiol.

View full text Add to dashboard Cite

Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen candidates for prime-boost vaccination strategies or extrapolated as markers for disease detection and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

Vemula

Ganji

Sivangala³

et al. 2016

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, in another study, 70% mutations were found in 306, 406 or 497 codons, 13% mutations outside the three regions between codons 296 and 426 and 15% mutations in the embC-embA intergenic region among the total 98% of mutations in the embCAB locus (Brossier et al, 2015 ). Recently, mutations in embB along with mutations in ubiA , encoding for a decaprenylphosphoryl-5-phosphoribose (DPPR) synthase associated with arabinogalactan synthesis pathway, were associated with high level of resistance to EMB (Tye et al, 2015 ).…”

Section: Molecular Targets Related Drug Resistance Mechanisms In Mdr-mentioning

confidence: 99%

Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains

Hameed

Islam

Chhotaray

et al. 2018

Front. Cell. Infect. Microbiol.

133

131

View full text Add to dashboard Cite

Tuberculosis (TB) is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting scenarios of multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and total drug-resistant tuberculosis (TDR-TB), due to number of resistance pathways, alongside some apparently obscure ones. Recent advances in the understanding of the molecular/ genetic basis of drug targets and drug resistance mechanisms have been steadily made. Intriguing findings through whole genome sequencing and other molecular approaches facilitate the further understanding of biology and pathology of M. tuberculosis for the development of new therapeutics to meet the immense challenge of global health.

show abstract

“…По результатам исследований [28][29][30] установлено, что появление мутаций в гене ubiA, кодирующего декапренилфосфорил-5-фосфорибоз-синтазу (биосинтез арабиногалактана), приводит к невосприимчивости M. tuberculosis к схеме лечения, включающей в себя декстро-2,2'-этилендиимин-ди-1-бу та нол (этам бутол).…”

Section: молекулярные механизмы устойчивости к этамбутолуunclassified

Mechanisms of development of medicine stability <i>Mycobacterium tuberculosis</i>: is there a chance to win?

Наумов

Павлунин

2021

Pulʹmonologiâ (Mosk.)

View full text Add to dashboard Cite

The scientific review provides current information on the current epidemiological status of tuberculosis in our country and the world, genetic adaptability and the evolution of Mycobacterium tuberculosis. The well-known and recently discovered molecular targets of aggression of this microorganism are described, and possible methods of circumventing the resistance of the Office to existing and developed drugs are presented. Objective: to create a scientific analytical review, which allows you to form an idea of the basic principles of development of the mechanisms of drug resistance of M. tuberculosis, as well as ways to overcome them with the possibility of further development of the chosen direction with the involvement of reputable scientific groups and practical implementation. Methods. scientific analysis of international reports, highly indexed scientific articles and clinical protocols. Results. Ihanks to the conducted analytical work, critical biological markers of M. tuberculosis immunity to anti-tuberculosis therapy were identified, which protect it from pharmacological intervention by the person and do not adequately sanitize the centers of inflammation in the patient's body. Methods have been proposed for disintegrating the mechanisms of drug resistance, which will bring the algorithms for treating tuberculosis infection to a new level. Conclusion. The analyzed information will contribute to deepening and expanding the knowledge of specialists involved in the fight against tuberculosis about the importance of implementing a personalized approach in the provision of medical care to TB patients, taking into account the studied molecular indicators of resistance to standardized and developed drugs.

show abstract

Vaccines for TB: Lessons from the Past Translating into Future Potentials

Cited by 10 publications

References 92 publications

Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains

Mechanisms of development of medicine stability <i>Mycobacterium tuberculosis</i>: is there a chance to win?

Contact Info

Product

Resources

About