scholarly journals Immunoinformatics and System Biology Approaches for Potential Vaccine Candidates Against Burkholderia Pseudomallei

2020 ◽  
Author(s):  
Asfiha Tarannum ◽  
Md. Arif Khan ◽  
Ahmad S. Sirajee ◽  
Mahmuda Yasmin ◽  
Chowdhury R. Ahsan
Keyword(s):  
System Biology ◽  
Burkholderia Pseudomallei ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Human Leukocyte ◽  
Protein Molecule ◽  
Dynamics Simulation ◽  
Vaccine Candidates ◽  
Potential Vaccine

Abstract Background: Burkholderia pseudomallei, an intracellular gram-negative bacterium, is the causative agent of melioidosis. It is a highly infectious disease that usually involves the lungs of humans as well as animals endemic in South-East Asia and Northern Australia. At present, we do not have any vaccine or treatment scheme at our disposal which is absolutely effective against this disease. There have been few advances in the development of vaccines against intracellular bacterial pathogens, making vaccine development against intracellular pathogen a more challenging arena. So, we opted for in-silico methods of drug designing intending to combat B. pseudomallei.Results: The whole proteome of B. pseudomallei was analyzed for determining immunogenic proteins. Combining B-cell and T-cell epitope prediction studies, the sequence ETAAADALY was considered as the most potential epitope for both T and B cells, followed by molecular docking against an MHC (major histocompatibility complex) Class I molecule, HLA-A*26:01 (human leukocyte antigens encoded by the HLA-A locus). Apart from epitope prediction, hydrogen bond study and target site analysis were carried out which concludes that ARG 237, ALA 234, ARG 236, ARG 262, GLN 226, ASP229, VAL 230, VAL 239, GLY 258, LEU259, ASN 225, and ILE 254 consist the best active site of the protein molecule. The study of the bacterial antigenic protein model's secondary structure and stereochemical properties provided an insight into the protein's stability as our epitope of choice. The post docking interactions were further subjected to molecular dynamics simulation and the system biology approach for validation. Conclusion: The goal of our endeavor is to delve into an integrative Immunoinformatics study combined with the system biology logistics of B. pseudomallei to detect potential vaccine candidates against this pathogen as well as providing a depiction of the bacterial immunome that could be insightful for vaccine generation in the future.

scholarly journals Role of Immunoinformatics in Accelerating Epitope-Based Vaccine Development against Dengue Virus

2020 ◽  
Vol 14 (1) ◽  
pp. 9-18
Author(s):  
Ahmad Husein Alkaff ◽  
Mutiara Saragih ◽  
Mochammad Arfin Fardiansyah ◽  
Usman Sumo Friend Tambunan
Keyword(s):  
Molecular Docking ◽  
Dengue Virus ◽  
Rational Design ◽  
Vaccine Development ◽  
Amino Acid Level ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Public Health Problem ◽  
Dynamics Simulation ◽  
Molecular Docking And Dynamics

Dengue Fever (DF) has emerged as a significant public health problem of international concern with its high prevalence in the tropic and subtropical regions. Dengue Virus (DENV), which is the cause of DF, consists of four serotypes of antigenically distinct viruses. The immense variation and limited identity similarity at the amino acid level lead to a problematic challenge in the development of an efficacious vaccine. Fortunately, the extensively available immunological data, the advance in antigenic peptide prediction, and the incorporation of molecular docking and dynamics simulation in immunoinformatics have directed the vaccine development towards the rational design of the epitope-based vaccine. Here, we point out the current state of dengue epidemiology and the recent development in vaccine development. Subsequently, we provide a systematic review of our validated method and tools for B- and T-cell epitope prediction as well as the use of molecular docking and dynamics in evaluating epitope affinity and stability in the discovery of a new tetravalent dengue vaccine through computational epitope-based vaccine design.

scholarly journals Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

2015 ◽  
Vol 7 ◽  
pp. III.S24755 ◽  
Author(s):  
Satarudra Prakash Singh ◽  
Vishal Verma ◽  
Bhartendu Nath Mishra
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Proteome Analysis ◽  
Effective Vaccine ◽  
Secretory Proteins ◽  
Vaccine Candidates ◽  
Proteome Level

Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.

scholarly journals Immunodominant linear B cell epitopes in the spike and membrane proteins of SARS-CoV-2 identified by immunoinformatics prediction and immunoassay

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanokporn Polyiam ◽  
Waranyoo Phoolcharoen ◽  
Namphueng Butkhot ◽  
Chanya Srisaowakarn ◽  
Arunee Thitithanyanont ◽  
...  
Keyword(s):  
B Cell ◽  
Cleavage Site ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
E Proteins ◽  
B Cell Epitopes ◽  
C Terminus ◽  
B Cell Epitope ◽  
Linear B

AbstractSARS-CoV-2 continues to infect an ever-expanding number of people, resulting in an increase in the number of deaths globally. With the emergence of new variants, there is a corresponding decrease in the currently available vaccine efficacy, highlighting the need for greater insights into the viral epitope profile for both vaccine design and assessment. In this study, three immunodominant linear B cell epitopes in the SARS-CoV-2 spike receptor-binding domain (RBD) were identified by immunoinformatics prediction, and confirmed by ELISA with sera from Macaca fascicularis vaccinated with a SARS-CoV-2 RBD subunit vaccine. Further immunoinformatics analyses of these three epitopes gave rise to a method of linear B cell epitope prediction and selection. B cell epitopes in the spike (S), membrane (M), and envelope (E) proteins were subsequently predicted and confirmed using convalescent sera from COVID-19 infected patients. Immunodominant epitopes were identified in three regions of the S2 domain, one region at the S1/S2 cleavage site and one region at the C-terminus of the M protein. Epitope mapping revealed that most of the amino acid changes found in variants of concern are located within B cell epitopes in the NTD, RBD, and S1/S2 cleavage site. This work provides insights into B cell epitopes of SARS-CoV-2 as well as immunoinformatics methods for B cell epitope prediction, which will improve and enhance SARS-CoV-2 vaccine development against emergent variants.

scholarly journals Preliminary Work Towards Finding Proteins as Potential Vaccine Candidates for Vibrio cholerae Pakistani Isolates through Reverse Vaccinology

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 195 ◽  
Author(s):  
Samia Zeb ◽  
Amjad Ali ◽  
Sardar Muhammad Gulfam ◽  
Habib Bokhari
Keyword(s):  
Vibrio Cholerae ◽  
Tertiary Structure ◽  
Diarrheal Disease ◽  
Vaccine Development ◽  
Protein A ◽  
Reverse Vaccinology ◽  
Whole Genome Sequence ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
Potential Vaccine

Background and Objective: Vibrio cholerae continues to emerge as a dangerous pathogen because of increasing resistance to a number of antibiotics. This paper provides a solution to emerging antibiotic resistance by introducing novel proteins as vaccine candidates against cholera. Materials and Methods: Vibrio cholerae genome versatility is a hurdle for developing a vaccine to combat diarrhoeal infection, so its core gene information was used to determine a potential vaccine candidate. Whole genome sequence data of more than 100 Vibrio cholerae strains were used simultaneously to get core genome information. The VacSol pipeline based on reverse vaccinology was selected to address the problem of safe, cheap, temperature-stable, and effective vaccine candidates which can be used for vaccine development against Vibrio cholerae. VacSol screens vaccine candidates using integrated, well-known, and robust algorithms/tools for proteome analysis. The proteomes of the pathogens were initially screened to predict homology using BLASTp. Proteomes that are non-homologous to humans are then subjected to a predictor for localization. Helicer predicts transmembrane helices for the protein. Proteins failing to comply with the set parameters were filtered at each step, and finally, 11 proteins were filtered as vaccine candidates. Results: This selected group of vaccine candidates consists of proteins from almost all structural parts of Vibrio cholerae. Their blast results show that this filtered group includes flagellin A protein, a protein from the Zn transporter system, a lipocarrier outer membrane protein, a peptidoglycan-associated protein, a DNA-binding protein, a chemotaxis protein, a tRNA Pseuriudine synthase A, and two selected proteins, which were beta lactamases. The last two uncharacterized proteins possess 100% similarity to V. albensis and Enterobacter, respectively. Tertiary structure and active site determination show a large number of pockets on each protein. Conclusions: The most interesting finding of this study is that 10 proteins out of 11 filtered proteins are introduced as novel potential vaccine candidates. These novel vaccine candidates can result in the development of cost-effective and broad-spectrum vaccines which can be used in countries where cholera is a major contributor to diarrheal disease.

Computational screening of potential MHC class I restricted cytotoxic T lymphocytes-based common multi-epitopes of major arboviral diseases

2020 ◽  
Vol 15 (8) ◽  
pp. 497-505
Author(s):  
Rakshanda Sajeed ◽  
Kishore Sarma ◽  
Kimmi Sarmah ◽  
Dipankar Biswas ◽  
Biswajyoti Borkakoty
Keyword(s):  
Mhc Class I ◽  
Vaccine Development ◽  
Health Hazard ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Class I ◽  
Population Coverage ◽  
Computational Screening ◽  
Antigenic Properties ◽  
Arboviral Diseases

Aim: Arboviral diseases are a health hazard and Flavivirus and Alphavirus infections are the most common in humans. This study focuses on immunoinformatic approaches to identify potential MHC class I restricted epitopes common for some selected arboviral diseases. Materials & methods: T-cell epitope prediction tool of Immune Epitope Database was employed to identify putative epitopes from the polyproteins of the selected viruses. Further, population coverage, conservancy, antigenic properties and docking analyses were performed to identify potential common epitopes for the selected viruses. Results: Eight common epitopes were screened for the selected viruses based on their population coverage, conservancy, antigenic properties and binding affinity. Conclusion: Considering the in silico potency, identified epitopes may further be subjected for candidate vaccine development against these arboviruses.

scholarly journals Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1327
Author(s):  
Azaz Ul Haq ◽  
Abbas Khan ◽  
Jafar Khan ◽  
Shamaila Irum ◽  
Yasir Waheed ◽  
...  
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Vaccine Development ◽  
Dynamic Properties ◽  
Dynamics Simulation ◽  
Strong Immune Response ◽  
Agent Based ◽  
Aliphatic Index ◽  
Structural Vaccinology ◽  
Potential Vaccine

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine–TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy.

scholarly journals Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by Mycobacterium bovis BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis

2004 ◽  
Vol 72 (11) ◽  
pp. 6471-6479 ◽  
Author(s):  
Hans Joachim Mollenkopf ◽  
Leander Grode ◽  
Jens Mattow ◽  
Maik Stein ◽  
Peggy Mann ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Mycobacterium Bovis ◽  
Protective Antigen ◽  
Epitope Prediction ◽  
Proteome Analysis ◽  
Vaccine Candidates ◽  
Boost Vaccination ◽  
Histocompatibility Complex ◽  
Potential Vaccine ◽  
Computational Predictions

ABSTRACT Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost “on top” of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.

scholarly journals Predicting and Designing Epitope Ensemble Vaccines against HTLV-1

2020 ◽  
Vol 16 (4) ◽  
Author(s):  
Saruar Alam ◽  
Md. Kamrul Hasan ◽  
Omar Hamza Bin Manjur ◽  
Akib Mahmud Khan ◽  
Zinat Sharmin ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Effective Vaccine ◽  
Binding Prediction ◽  
Multiple Sequence ◽  
T Lymphotropic Virus ◽  
Dynamics Simulations ◽  
Epitope Binding

AbstractThe infection mechanism and pathogenicity of Human T-lymphotropic virus 1 (HTLV-1) are ambiguously known for hundreds of years. Our knowledge about this virus is recently emerging. The purpose of the study is to design a vaccine targeting the envelope glycoprotein, GP62, an outer membrane protein of HTLV-1 that has an increased number of epitope binding sites. Data collection, clustering and multiple sequence alignment of HTLV-1 glycoprotein B, variability analysis of envelope Glycoprotein GP62 of HTLV-1, population protection coverage, HLA-epitope binding prediction, and B-cell epitope prediction were performed to predict an effective vaccine. Among all the predicted peptides, ALQTGITLV and VPSSSTPL epitopes interact with three MHC alleles. The summative population protection coverage worldwide by these epitopes as vaccine candidates was found nearly 70%. The docking analysis revealed that ALQTGITLV and VPSSSTPL epitopes interact strongly with the epitope-binding groove of HLA-A*02:03, and HLA-B*35:01, respectively, as this HLA molecule was found common with which every predicted epitope interacts. Molecular dynamics simulations of the docked complexes show they form stable complexes. So, these potential epitopes might pave the way for vaccine development against HTLV-1.

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