23
DOI: https://doi.org/10.1186/s43141-022-00411-7
English
eng
Lemes, Marcela Rezende
Contributor
<div id="abs0005" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0010" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Background</h3><div class="u-margin-s-bottom" id="sp0035" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">Leprosy is caused by <span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/mycobacteria" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Mycobacterium</a> leprae</span> and <span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/mycobacteria" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Mycobacterium</a></span><em style="margin: 0px; padding: 0px;"> lepromatosis</em></span>. Most of the affected population lives in low-income countries and may take up to 10 years to show any clinical signs, which is how physicians diagnose it. However, due to progressive cell damage, early diagnosis is very important. The best way to confirm leprosy is through bacilloscopic, which only confirms the diagnosis and has low accuracy or PCR, that requires specialized operators and is expensive. Since the bacteria are fastidious and do not grow in any culture media, therefore, diagnosing leprosy in the lab is still a challenge. In this concern, a recombinant multi-epitope protein can be a beneficial strategy in the management of the diagnosis, as diverse immunogenic epitopes are precisely selected to detect specific antibodies. Therefore, the purposes of the present study were to select immunogenic epitopes from different relevant proteins, with immunogenic properties, and then to construct a recombinant multi-epitope protein that accuses the presence of the antibodies in the early stages of the disease, making it more than appropriate to be applied as a diagnostic tool.</div></div><div id="abs0010" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0015" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0040" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><span style="margin: 0px; padding: 0px;">We selected 22 common proteins from both species and, using bioinformatics tools, predicted B and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/t-cell" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">T cell</a><span style="margin: 0px; padding: 0px;"> epitopes. After multiple filtering and analyzing, we ended up with 29 epitopes {MHC-I (total 18) and MHC-II (total 11)} from 10 proteins, which were then merged into one construct. Its secondary and <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tertiary-structure" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">tertiary structures</a> were also predicted and refined to comprise the </span></span><a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/amino-acid" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">amino acid</a> residues in the best conformation possible. The multi-epitope protein construct was stable, non-host homologous, non-allergic, non-toxic, and elicit humoral and cellular responses. It has conformational B cell epitopes and potential to elicit IFN-γ, IL-4, and IL-10 secretion.</div></div><div id="abs0015" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0020" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Conclusions</h3><div class="u-margin-s-bottom" id="sp0045" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">This novel recombinant multi-epitope protein constructed using the common epitopes from <em style="margin: 0px; padding: 0px;">M. leprae</em> and <em style="margin: 0px; padding: 0px;">M. lepromatosis</em><span style="margin: 0px; padding: 0px;"> has a huge immunological potential, is stable, and can be lyophilized to be used in <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/enzyme-linked-immunosorbent-assay" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration-line: underline; text-decoration-thickness: 1px; text-decoration-color: rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">ELISA</a> plates or even in biosensors, which are user-friendly diagnosis tools, facilitating translation into human sample tests.</span></div></div>
Elsevier
December 2022
pdf
Journal of Genetic Engineering and Biotechnology
In silico designing of a recombinant multi-epitope antigen for leprosy diagnosis
mixed material
Elsevier