Jundishapur Journal of Microbiology Jundishapur Journal of Microbiology Jundishapur J Microbiol http://www.jjmicrobiol.portal.tools 2008-3645 2008-4161 10.5812/jjm en jalali 2019 9 17 gregorian 2019 9 17 10 3
en 10.5812/jjm.43950 Designing a Novel Multi-epitope DNA- Based Vaccine Against Tuberculosis: In Silico Approach Designing a Novel Multi-epitope DNA- Based Vaccine Against Tuberculosis: In Silico Approach research-article research-article Conclusions

The results revealed that the novel multi-epitope DNA construct could be an effective candidate in tuberculosis vaccine development, and it is qualified to investigate its potential to induce CD4 and CD8 T- cell immune response in the experimental animal model.

Results

MHC class I-and class II-predicted epitopes showed a high potential to binding to human HLAs alleles, with global broad-spectrum population coverage. The construct had no allergenicity, and the analysis indicated a desirable antigenicity of the construct. The construct had several posttranslational modifications, no signal peptide, and cytoplasmic localization with high score. Also, mRNA analysis showed low ∆G which demonstrated high stability and efficient translation.

Background

Tuberculosis remains a major global threat. Two billion of the world’s population is latently infected with Mycobacterium tuberculosis and is at the risk of progression to active disease. Bacillus Calmette-Guerin (BCG), as the only licensed vaccine, has prophylaxis strategy, which protects children from disseminated form of tuberculosis. Therefore, postexposure vaccine strategy, which targets individuals with latent tuberculosis infection, is an important strategy to control this disease globally.

Methods

A mouse construct was designed based on predicted MHC class I-and class II-restricted T- cell epitopes that fused together tandemly. MHC class I-and class II-restricted epitopes were linked by AAY and GPGPG motifs, respectively. LC3 directly fused to the MHC class II-restricted epitopes at the C-terminus of the peptide. The varieties of expressed construct features were analyzed by bio- informatics tools. Finally, construct codons were optimized and mRNA structure of optimized construct was analyzed.

Objectives

In the present study, we designed a novel postexposure multi-epitope DNA construct based on 3 latency-associated antigens of Rv2029c, Rv2031c, and Rv2627c and microtubule-associated protein light chain 3 (LC3) as a hallmark protein of the autophagy system.

Conclusions

The results revealed that the novel multi-epitope DNA construct could be an effective candidate in tuberculosis vaccine development, and it is qualified to investigate its potential to induce CD4 and CD8 T- cell immune response in the experimental animal model.

Results

MHC class I-and class II-predicted epitopes showed a high potential to binding to human HLAs alleles, with global broad-spectrum population coverage. The construct had no allergenicity, and the analysis indicated a desirable antigenicity of the construct. The construct had several posttranslational modifications, no signal peptide, and cytoplasmic localization with high score. Also, mRNA analysis showed low ∆G which demonstrated high stability and efficient translation.

Background

Tuberculosis remains a major global threat. Two billion of the world’s population is latently infected with Mycobacterium tuberculosis and is at the risk of progression to active disease. Bacillus Calmette-Guerin (BCG), as the only licensed vaccine, has prophylaxis strategy, which protects children from disseminated form of tuberculosis. Therefore, postexposure vaccine strategy, which targets individuals with latent tuberculosis infection, is an important strategy to control this disease globally.

Methods

A mouse construct was designed based on predicted MHC class I-and class II-restricted T- cell epitopes that fused together tandemly. MHC class I-and class II-restricted epitopes were linked by AAY and GPGPG motifs, respectively. LC3 directly fused to the MHC class II-restricted epitopes at the C-terminus of the peptide. The varieties of expressed construct features were analyzed by bio- informatics tools. Finally, construct codons were optimized and mRNA structure of optimized construct was analyzed.

Objectives

In the present study, we designed a novel postexposure multi-epitope DNA construct based on 3 latency-associated antigens of Rv2029c, Rv2031c, and Rv2627c and microtubule-associated protein light chain 3 (LC3) as a hallmark protein of the autophagy system.

Bioinformatics;Latency-Associated Antigen;LC3;T- Cell Epitope;DNA Vaccine Bioinformatics;Latency-Associated Antigen;LC3;T- Cell Epitope;DNA Vaccine http://www.jjmicrobiol.portal.tools/index.php?page=article&article_id=43950 Jale Moradi Jale Moradi Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Mina Tabrizi Mina Tabrizi Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Maryam Izad Maryam Izad Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran Nader Mosavari Nader Mosavari Department of Tuberculosis, Razi Vaccine and Serum Research Institute, Karaj, IR Iran Department of Tuberculosis, Razi Vaccine and Serum Research Institute, Karaj, IR Iran Mohammad Mehdi Feizabadi Mohammad Mehdi Feizabadi Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran; Thoracic Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, IR Iran; Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2188955810 Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran; Thoracic Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, IR Iran; Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2188955810