Proteome Exploration of <i>Legionella pneumophila</i> for Identifying Novel Therapeutics: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

Khan, Md. Tahsin; Mahmud, Araf; Hasan, Mahmudul; Azim, Kazi Faizul; Begum, Musammath Kulsuma; Akter, Arzuba; Mondal, Shakhinur Islam

doi:10.1101/2020.02.03.922864

Cited by 3 publications

(2 citation statements)

References 126 publications

(111 reference statements)

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“…An AAY linker was utilized to separate CTL epitopes, while the GPGPG linker and KK linker were employed to attach the HTL and BCL epitopes, respectively [ 91 ]. In addition, an EAAAK linker separated the L7/L12 Ribosomal protein, a Toll-like receptor-4 (TLR-4) agonist [ 92 ], from the universal PADRE sequence at the N-terminal end of the vaccine [ 93 ]. An EGGE linker joined the invasin peptide with another PADRE sequence at the C-terminal end of the vaccine [ 94 ].…”

Section: Methodsmentioning

confidence: 99%

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

Khan,

Mahmud,

Islam

et al. 2023

Genomics Inform

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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

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Section: Methodsmentioning

confidence: 99%

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

Khan,

Mahmud,

Islam

et al. 2023

Genomics Inform

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“…Different beneficial activities of the human microbiome were reported, and the link between gut flora and humans is not only commensal but symbiotic, mutualistic [60]. The host may experience negative consequences if proteins in this microbiota are blocked or inhibited inadvertently.…”

Section: Non-homolog Gut Protein Identificationmentioning

confidence: 99%

Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

2022

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Brucella suis mediates the transmission of brucellosis in humans and animals and a significant facultative zoonotic pathogen found in livestock. It has the capacity to survive and multiply in a phagocytic environment and to acquire resistance under hostile conditions thus becoming a threat globally. Antibiotic resistance is posing a substantial public health threat, hence there is an unmet and urgent clinical need for immune-based non-antibiotic methods to treat brucellosis. Hence, we aimed to explore the whole proteome of Brucella suis to predict antigenic proteins as a vaccine target and designed a novel chimeric vaccine (multi-epitope vaccine) through subtractive genomics-based reverse vaccinology approaches. The applied subsequent hierarchical shortlisting resulted in the identification of Multidrug efflux Resistance-nodulation-division (RND) transporter outer membrane subunit (gene BepC) that may act as a potential vaccine target. T-cell and B-cell epitopes have been predicted from target proteins using a number of immunoinformatic methods. Six MHC I, ten MHC II, and four B-cell epitopes were used to create a 324-amino-acid MEV construct, which was coupled with appropriate linkers and adjuvant. To boost the immunological response to the vaccine, the vaccine was combined with the TLR4 agonist HBHA protein. The MEV structure predicted was found to be highly antigenic, non-toxic, non-allergenic, flexible, stable, and soluble. To confirm the interactions with the receptors, a molecular docking simulation of the MEV was done using the human TLR4 (toll-like receptor 4) and HLAs. The stability and binding of the MEV-docked complexes with TLR4 were assessed using molecular dynamics (MD) simulation. Finally, MEV was reverse translated, its cDNA structure was evaluated, and then, in silico cloning into an E. coli expression host was conducted to promote maximum vaccine protein production with appropriate post-translational modifications. These comprehensive computer calculations backed up the efficacy of the suggested MEV in protecting against B. suis infections. However, more experimental validations are needed to adequately assess the vaccine candidate's potential. Highlights• Subtractive genomic analysis and reverse vaccinology for the prioritization of novel vaccine target • Examination of chimeric vaccine in terms of allergenicity, antigenicity, MHC I, II binding efficacy, and structural-based studies • Molecular docking simulation method to rank based vaccine candidate and understand their binding modes

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Proteome Exploration of Human Coronaviruses for Identifying Novel Vaccine Candidate: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

Dorosti

Zarei

Nezafat

2023

BIOT

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Background: The SARSCoV-2 is responsible for infecting more than 271,000,000 people in 222 countries by December 10, of which 5,300,000 have died. COVID-19 was introduced by World Health Organization as a global concern and a pandemic disease due to the prevalence of disease. Objectives: Developing of preventive or therapeutics medication against novel-cov2019 is an urgent need, and has high priority among scientific societies, in this regard, the production of effective vaccines is one of the most significant and high-priority necessity. To date specific antiviral therapeutic and prophylactic vaccine for novel coronavirus (n-CoV2019) are not available. Because of costing and time-consuming of experimental strategies during vaccine design procedure, different immunoinformatics methods were developed. Recently Because of defect study on proteins of n-cov2019, its recommended to study other human coronaviruses. Methods: At the beginning of vaccine design, the proteome study is essential. In this investigation, the whole human coronaviruses proteome was evaluated using proteome subtraction strategy. Out of 5945 human coronavirus proteins, five new antigenic proteins were selected by analyzing the hierarchical proteome subtraction and then their various physicochemical and immunological properties were also investigated bioinformatically. Results: All five protein sequences are antigenic and non-allergenic proteins; moreover, spike protein group including Spike glycoprotein (E2) (Peplomer protein), spike fragment and spike glycoprotein fragment showed acceptable stability, which can be used to design new vaccines against human coronaviruses. Conclusion: These selected peptides and the other introduced protein in this study (HE, orf7a, SARS_X4 domain-containing protein and protein 8) can be employed as a suitable candidate for developing novel prophylactic or therapeutic vaccine against human coronaviruses.

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Proteome Exploration of Legionella pneumophila for Identifying Novel Therapeutics: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

Cited by 3 publications

References 126 publications

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

Proteome Exploration of Human Coronaviruses for Identifying Novel Vaccine Candidate: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

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