An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) is a highly contagious disease that mostly affects the lungs and is caused by a bacterial pathogen, Mycobacterium tuberculosis. The associated mortality rate of TB is much higher compared to any other disease and the situation is more worrisome by the rapid emergence of drug resistant strains. Bacillus Calmette–Guerin (BCG) is the only licensed attenuated vaccine available for use in humans however, many countries have stopped its use as it fails to confer protective immunity. Therefore, urgent efforts are required to identify new and safe vaccine candidates that are not only provide high immune protection but also have broad spectrum applicability. Considering this, herein, I performed an extensive computational vaccine analysis to investigate 200 complete sequenced genomes of M. tuberculosis to identify core vaccine candidates that harbor safe, antigenic, non-toxic, and non-allergic epitopes. To overcome literature reported limitations of epitope-based vaccines, I carried out additional analysis by designing a multi-epitopes vaccine to achieve maximum protective immunity as well as to make experimental follow up studies easy by selecting a vaccine that can be easily analyzed because of its favorable physiochemical profile. Based on these analyses, I identified two potential vaccine proteins that fulfill all required vaccine properties. These two vaccine proteins are diacylglycerol acyltransferase and ESAT-6-like protein. Epitopes: DSGGYNANS from diacylglycerol acyltransferase and AGVQYSRAD, ADEEQQQAL, and VSRADEEQQ from ESAT-6-like protein were found to cover all necessary parameters and thus used in a multi-epitope vaccine construct. The designed vaccine is depicting a high binding affinity for different immune receptors and shows stable dynamics and rigorous van der Waals and electrostatic binding energies. The vaccine also simulates profound primary, secondary, tertiary immunoglobulin production as well as high interleukins and interferons count. In summary, the designed vaccine is ideal to be evaluated experimentally to decipher its real biological efficacy in controlling drug resistant infections of M. tuberculosis.

Peptide-Based Vaccines for Tuberculosis

“…Therefore, enhancing host immune responses with TLR2 and TLR4 agonists may be the option for constructing an ideal peptide-based vaccine in future. At present, some TLR2 and TLR4 agonists have been used in peptide-based vaccines against infectious diseases, including TB, such as TLR2 agonists ESAT6 ( 144 ), phenol-soluble modulin α4 (PSMα4) ( 145 ), dipalmitoyl-S-glyceryl cysteine (Pam2Cys) ( 115 , 146 ), and PorB ( 147 , 148 ), TLR4 agonists RpfE (Rv2450c) ( 149 ), 50S ribosomal protein L7/L12 (RplL) ( 22 , 150 – 155 ), heparin binding hemagglutinin (HBHA) ( 156 ), cholera toxin subunit B (CTB) ( 157 – 159 ), and RS-09 ( 160 , 161 ). In addition, helper peptides and antimicrobial peptides are also used to construct peptide-based vaccines to enhance their immune effects, such as PADRE ( 148 ) ( 151 ) ( 156 ), Hsp70 ( 161 ), TR-433 ( 161 ), human β-defensin 1 (HBD-1) ( 162 ), HBD-2 ( 163 ), HBD-3 ( 19 , 164 – 167 ), and Griselimycin ( 84 ).…”

Developing a multiepitope vaccine for the prevention of SARS-CoV-2 and monkeypox virus co-infection: A reverse vaccinology analysis

“…A novel multiepitope vaccine was constructed by linking immunodominant CTL, HTL, and B-cell epitopes using AAY, GPGPG, and KK linkers, respectively. To improve the antigenicity and immunogenicity of this multiepitope vaccine, the toll-like receptor 4 (TLR4) agonist RS-09 [41] and a 13 amino acid nonnatural pan DR epitope (PADRE) were added to the amino terminus of the multiepitope vaccine, and the TLR2 agonist dipalmitoyl-S-glycero-cysteine (Pam2Cys) and a 6× His tag (HHHHH) were added to its carboxyl terminus [42] , [43] . TLR agonists and PADRE were linked to epitopes using an EAAAK linker.…”

Recent Advances in Genomics-Based Approaches for the Development of Intracellular Bacterial Pathogen Vaccines

“…These two vaccines exhibited rigorous van der Waals and electrostatic binding forces, stable dynamics, and high binding affinities for several immunological receptors. The researchers noticed remarkable primary, secondary, and tertiary immune responses to the antigens in addition to a raised interleukin and interferon count [ 129 ]. In conclusion, the proposed vaccines appear to be viable candidates for further evaluation.…”