Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology

Abstract

Tuberculosis (TB) is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG) vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment) prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines.

In silico-based vaccine design against Ebola virus glycoprotein

“…As a corollary, UniProtKB id: Q9YMG2 was identified as the most potent antigenic protein having a maximum total prediction score of 0.5390. Here the threshold of 0.5 is considered as the potent antigenicity 55. This sequence was used for further analysis.…”

Protein expression of Myt272-3 recombinant clone and in silico prediction of a possible vaccine candidate against <i>Mycobacterium tuberculosis</i>

“…It is known that vaccines are considered good when they do not show homology with human proteins, thus eliminating likelihood of their triggering on autoimmune response [8].…”

“…In addition, BCG has shown protective efficacies in adult pulmonary tuberculosis, ranging from 0 to 80 per cent [7]. Identification of microbial components responsible for generation of immune responses is the first and most crucial step in the development of new vaccines [8]. Immunoinformatics deals with the application of bioinformatics in immunology and is widely accepted due to its usefulness in the design of new vaccines through identification of T-cell epitope, B-cell epitopes and MHCs [9].…”

The Impact of Bioinformatics on Vaccine Design and Development

“…Once the genome sequence is obtained, it is possible to identify all likely proteins that could be expressed. For this purpose, several software systems and programs identify all open reading frames (ORFs) that constitute the sequences expressing the majority of proteins [8][9][10].…”

“…The number of new cases worldwide rose to 10.4 million [42]; this high incidence rate is based on several factors, and one of the most important factors is the inefectiveness of the vaccine used at present: the BCG. Thus, why many working groups are investigating new vaccines that can improve the level of protection against this disease, and one of the tools utilized is reverse vaccinology [10].…”