Abstract
In general, the members of Lip gene family of Mycobacterium tuberculosis evoke strong immune response in the host. Keeping this fact into consideration, we investigated role of Rv3203, a cell wall associated protein with lipolytic activity, in imparting protection against experimental murine tuberculosis. The data of the present study suggested that archaeosome encapsulated Rv3203 induce strong lymphocyte proliferation, up-regulated Th-1 biased cytokines profile, increased expression of co-stimulatory markers on both antigen presenting cells and T lymphocytes. The immuno-prophylactic response was further modulated by exposure of the animals to zymosan, a TLR2/6 agonist, prior to immunization with archaeosome encapsulated Rv3203. Interestingly, pre-treatment of experimental animals with zymosan boosted strong immunological memory as compared to archaeosome encapsulated Rv3203 as well as BCG vaccine. We conclude that priming of immunized animal with TLR agonist followed by immunization with archaeosomes encapsulated Rv3203 offer substantial protection against tuberculosis infection and could be a potential subunit vaccine based prophylactic strategy.
Highlights
The pathogen Mycobacterium tuberculosis (M. tuberculosis), the etiologic agent of human tuberculosis (TB), has been estimated to inflict around 9.6 million people (5.4 million men, 3.2 million women and 1.0 million children) world-wide up to the year 2014 [1,2]
Employing immuno-informatics analysis, Rv3203 was predicted as a cytosolic protein; the immune-localization studies performed with specific polyclonal antibodies suggested that the enzyme is mainly confined to the cell wall fraction of M. tuberculosis
We infer that archaeosomes based Rv3203 can successfully confer long lasting and effective protection against experimental murine tuberculosis
Summary
The pathogen Mycobacterium tuberculosis (M. tuberculosis), the etiologic agent of human tuberculosis (TB), has been estimated to inflict around 9.6 million people (5.4 million men, 3.2 million women and 1.0 million children) world-wide up to the year 2014 [1,2]. Underlying these statistics is an emerging epidemic of multidrug-resistant tuberculosis (MDR-TB) and extremely drug resistance TB (XDR-TB) [1,2,3]. To subsist, during the hostile intracellular abode, in macrophages is generally attributed to its ability to modulate host immune responses in its favour [4]. There has been a global effort to solve intricacies of the complex interaction between the M. tuberculosis and the host, as pathogen can shift into a dormant non-replicating status causing a latent TB infection [5]
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