Abstract
Tuberculosis is one the oldest known affliction of mankind caused by the pathogen Mycobacterium tuberculosis. Till date, there is no absolute single treatment available to deal with the pathogen, which has acquired a great potential to develop drug resistance rapidly. BCG is the only anti-tuberculosis vaccine available till date which displays limited global efficacy due to genetic variation and concurrent pathogen infections. Extracellular vesicles or exosomes vesicle (EVs) lie at the frontier cellular talk between pathogen and the host, and therefore play a significant role in establishing pathogenesis. In the present study, an in-silico approach has been adopted to construct a multi-epitope vaccine from selected immunogenic EVs proteins to elicit a cellular as well as a humoral immune response. Our designed vaccine has wide population coverage and can effectively compensate for the genetic variation among different populations. For maximum efficacy and minimum adverse effects possibilities the antigenic, non-allergenic and non-toxic B-cell, HTL and CTL epitopes from experimentally proven EVs proteins were selected for the vaccine construct. TLR4 agonist RpfE served as an adjuvant for the vaccine construct. The vaccine construct structure was modelled, refined and docked on TLR4 immune receptor. The designed vaccine construct displayed safe usage and exhibits a high probability to elicit the critical immune regulators, like B cells, T-cells and memory cells as displayed by the in-silico immunization assays. Therefore, it can be further corroborated using in vitro and in vivo assays to fulfil the global need for a more efficacious anti-tuberculosis vaccine.
Highlights
Tuberculosis is one the oldest known affliction of mankind caused by the pathogen Mycobacterium tuberculosis
In light of ever-expanding drug resistance and adverse effects associated with anti-TB drugs such as ototoxicity, hepatotoxicity, neuropsychiatricevents, hyperuricemia, gastrointestinal disturbance, vision loss, skin pigmentation etc[52], a safe and efficacious vaccine could be an imperative arsenal against this deadly disease
The utilization of different media may result in a variation to BCG efficacy, as there are shreds of evidences that proves that BCG cultured in Sauton media have better immunogenicity than the BCG cultured in Middlebrook 7H9 medium[55]
Summary
Tuberculosis is one the oldest known affliction of mankind caused by the pathogen Mycobacterium tuberculosis. BCG is the only anti-tuberculosis vaccine available till date which displays limited global efficacy due to genetic variation and concurrent pathogen infections. An in-silico approach has been adopted to construct a multi-epitope vaccine from selected immunogenic EVs proteins to elicit a cellular as well as a humoral immune response. The designed vaccine construct displayed safe usage and exhibits a high probability to elicit the critical immune regulators, like B cells, T-cells and memory cells as displayed by the in-silico immunization assays It can be further corroborated using in vitro and in vivo assays to fulfil the global need for a more efficacious anti-tuberculosis vaccine. Proteolysis of bacterial molecules by phagolysosome can generate peptides that can be antigenic or immunogenic and carried out by EVs. In the present study, we have selected seven secreted mycobacterial proteins (DnaK, GrpE, LpqH, HBHA, LprA, LprG and MPT83) and a TLR4 agonist RpfE as vaccine adjuvant. MPT83 (Rv2873) is a secreted mycobacterial lipo-glycoprotein which is recognised by TLR2 and induces innate and adaptive immune response through the elevated level of cytokines like TNF-α, IL-6, IL-12 p40 and IFN-α25
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