| Popis: |
Human pulmonary tuberculosis represents an unfortunately placed and persistent thorn in global health; asymptomatically infecting nearly a third of the global population, with roughly 10 million new cases and 1.5 million deaths annually. It continues to hold a place among the top ten causes of death in the world and remains the leading infectious cause of death by a single pathogen. Among the numerous reasons for such statistics is the relatively poor efficacy of the near-century-old BCG vaccine. In spite of it being the only approved vaccine for TB, its benefit is predominantly observed in preventing paediatric miliary TB and TB meningitis, whilst it offers considerably limited protection against infection in adults. The advent of mRNA vaccine technologies has passed the critical tribulations for current demand of Coronavirus disease 2019, and in so validating the argument on employing the technology as an effective response to TB as it suggests fulfilment of the necessary criteria: induction of robust, determined innate response with a favourable safety profile across a wider population. To this end, the novel mRNA vaccines were proven to elicit immune responses against bacterial pathogens; by virtue, the technology may be applied in bacterial infection treatment. Meanwhile, no approved mRNA prophylactics for bacterial infections exist yet. Within this work, we propose a novel vaccine design for TB that harvests the potential of mRNA vaccine technology. This was achieved by using a barrage of in silico tools for epitope identification, construct design and rigorous physicochemical evaluation and immune response predictions. The vaccine itself was design for the purpose of immunizing previously unexposed patients, along with individuals that have asymptomatic TB. Additionally, immune response simulations have predicted an immune response relatively in agreement with the natural, beneficial, response to M.tb infection, rather than the detrimental variety. |
