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Improving the efficacy of bacillus calmette guerin vaccine by concomitant inhibition of T regulatory and T helper 2 cells.

dc.contributor.advisorMoodley, Prashini.
dc.contributor.advisorDas, Gobardhan.
dc.contributor.authorKumar, Santosh.
dc.date.accessioned2017-06-21T08:06:28Z
dc.date.available2017-06-21T08:06:28Z
dc.date.created2015
dc.date.issued2015
dc.descriptionDoctor of Philosophy in Medical Microbiology. University of KwaZulu-Natal, Medical School 2015.en_US
dc.description.abstractTuberculosis (TB) remains a major threat to human population as currently Mycobacterium tuberculosis (MTB) infects nearly 33% of the global population. Annually, about one and a half million deaths are caused by tuberculosis (TB). Current reports suggest that approximately nine million new TB cases are reported every year. There is an available therapy for TB, however it is quite lengthily and consists of numerous antibiotics leading to treatment dropout. This treatment incompletion has been linked to the major cause for the appearance of drug-resistant species of MTB. Consequently, alternate therapies to treat TB are needed. Bacillus Calmette-Guerin (BCG) remains the only vaccine of choice since its inception in 1921. Although BCG mounts host protective T helper1 (Th1) cell activation, which plays a pivotal role in host protection against TB, its efficacy is inadequate, suggesting that additional methods to enhance protective immune responses are needed. We have also shown that simultaneous inhibition of Th2 cells and Tregs by using pharmacological inhibitors (suplatasttosylate and D4476, respectively) dramatically enhance MTB clearance and induces a superior Th1 response. Here we show that treatment with these two immuno-modulators during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in T cell memory development, towards central memory T (Tcm) cell responses. Collectively, our findings provide evidence that concurrent inhibition of T helper cells type 2 and Tregs during BCG vaccination promotes vaccine efficacy.en_US
dc.identifier.urihttp://hdl.handle.net/10413/14643
dc.language.isoen_ZAen_US
dc.subjectBCG vaccines.en_US
dc.subjectT cells--Differentiation.en_US
dc.subjectMycobacterium tuberculosis.en_US
dc.subjectTheses--Medical microbiology.en_US
dc.subjectBacillus Calmette-Guérin vaccines.en_US
dc.titleImproving the efficacy of bacillus calmette guerin vaccine by concomitant inhibition of T regulatory and T helper 2 cells.en_US
dc.typeThesisen_US

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