scholarly journals Designing of a novel multisubunit vaccine against Nipah virus structural proteins: A reverse vaccinology approach

2021 ◽  
Author(s):  
khalid Mohamed Adam
Keyword(s):  
Nipah Virus ◽  
Reverse Vaccinology ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Compact Structure ◽  
Grand Average ◽  
Physiochemical Parameters ◽  
Significant Public Health ◽  
Aliphatic Index ◽  
Stable Molecule

Abstract Background The significant public health risk posed by NiV zoonosis and the lack of effective countermeasures against the intermittent outbreaks of the disease in the South and Southeast Asia region have entailed an imperative search for a protective vaccine to prevent or mitigate its epidemic potentiality. This is an endeavor to design an effective, safe multisubunit vaccine using an in silico reverse vaccinology approach. Methods The epitopes used for the construction of the candidate vaccine were meticulously predicted from five viral structural proteins (G, F, M, N, P) using several immunoinformatics tools to assess different epitope characteristics, namely, VaxiJen server for antigenicity, IEDB immunogenicity tool for immunogenicity, AlgPred server for allergenicity, ToxinPred for toxigenicity, IFNepitope server for interferon-gamma induction, Protparam server for physicochemical properties, GROMACS for simulation and simulation dynamics analysis, and finally, SnapGene tool for molecular cloning. Results The proposed vaccine molecule consisted of 501 amino acids, encompassing 7 B cell epitopes, 14 CTL epitopes, and 4 HTL epitopes. The physiochemical parameters of the vaccine construct showed a molecular weight of 54.6 kDa, an acidic stable molecule with an instability index of 38.3, aliphatic index of 62.89, and grand average of hydropathicity of -0.476. Moreover, the docking results and simulation dynamics of the vaccine molecule and TLR-3 showed global energy of 1.58 Kcal/mol, atomic contact energy of 2.98 Kcal/mol, and RMSD of 0.65 nm. The radius gyration showed a relatively steady value throughout the simulation period. a suggestive result of a stable compact structure and a promisingly effective vaccine construct. Conclusion In summary, the overall results of the multi-subunit vaccine molecule are suggestive of a promisingly effective vaccine against NiV infection in humans with a relatively stable compact structure, however, further experimental validation and assessment of pathogenic priming and autoimmunity induction are recommended.

scholarly journals Vaccinomic approach for novel multi epitopes vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yassir A. Almofti ◽  
Khoubieb Ali Abd-elrahman ◽  
Elsideeq E. M. Eltilib
Keyword(s):  
Binding Energy ◽  
T Lymphocytes ◽  
Severe Acute Respiratory Syndrome ◽  
Tertiary Structure ◽  
Effective Vaccine ◽  
S Protein ◽  
Grand Average ◽  
Aliphatic Index ◽  
Novel Coronavirus ◽  
B And T Lymphocytes

Abstract Background The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers. Results The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was − 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of − 338.68 kcal/mol and − 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression. Conclusion A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.

T-cell Epitope-based Vaccine Design for Nipah Virus by Reverse Vaccinology Approach

2020 ◽  
Vol 23 (8) ◽  
pp. 788-796
Author(s):  
Praveen K.P. Krishnamoorthy ◽  
Sekar Subasree ◽  
Udhayachandran Arthi ◽  
Mohammad Mobashir ◽  
Chirag Gowda ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Nipah Virus ◽  
3D Structure ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Reverse Vaccinology ◽  
Stable Complex

Aim and Objective: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and Methods: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T – cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T – cells. Conclusion: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

Bioinformatics Analysis of Laccase (Lac1) in Pycnoporus cinnabarinus

2010 ◽  
Vol 121-122 ◽  
pp. 502-506
Author(s):  
He Li ◽  
Guo Ying Zhou ◽  
Huai Yun Zhang ◽  
Liang Guo
Keyword(s):  
Amino Acid ◽  
Manganese Peroxidase ◽  
Bioinformatics Analysis ◽  
Instability Index ◽  
Pycnoporus Cinnabarinus ◽  
Grand Average ◽  
Glycosylation Sites ◽  
The World ◽  
Aliphatic Index

Pycnoporus cinnabarinus is a plant pathogen. It is common in many areas and is widely distributed throughout the world. Laccases of are some of the few oxidoreductases commercialized as industrial catalysts. In the present study, some characters of the amino acid sequence of P.cinnabarinus laccase (Lac1) were predicted and analyzed with the tools of bioinformatics. These results showed that the protein was composed of 20 kinds of amino acid; the theoretical pI of manganese peroxidase was 4.81 and the theoretical molecular weight of manganese peroxidase was 56292.0 Da; total number of atoms was 7806; the extinction coefficient was 58120 (280 nm). The N-terminal of the sequence considered was M (Met) and the estimated half-life was 30 hours (mammalian reticulocytes, in vitro). The instability index (II) was computed to be 34.50; this classifies the protein as stable. Aliphatic index was 82.64. Grand average of hydropathicity (GRAVY) was -0.063. There were 8 glycosylation sites, a signal peptide and conserved domains.

scholarly journals Evaluating Replication-Defective Vesicular Stomatitis Virus as a Vaccine Vehicle

2006 ◽  
Vol 80 (14) ◽  
pp. 6993-7008 ◽  
Author(s):  
Ayaz M. Majid ◽  
Heather Ezelle ◽  
Sangeeta Shah ◽  
Glen N. Barber
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Cell Activity ◽  
Recombinant Vaccinia Virus ◽  
Antibody Responses ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Murine Models ◽  
Vesicular Stomatitis ◽  
Ifn Γ ◽  
Hcv Structural Proteins

ABSTRACT We have generated replication-competent (VSV-C/E1/E2) and nonpropagating (VSVΔG-C/E1/E2) vesicular stomatitis virus (VSV) contiguously expressing the structural proteins of hepatitis C virus (HCV; core [C] and glycoproteins E1 and E2) and report on their immunogenicity in murine models. VSV-C/E1/E2 and VSVΔG-C/E1/E2 expressed high levels of HCV C, E1, and E2, which were authentically posttranslationally processed. Both VSV-expressed HCV E1-E2 glycoproteins were found to form noncovalently linked heterodimers and appeared to be correctly folded, as confirmed by coimmunoprecipitation analysis using conformationally sensitive anti-HCV-E2 monoclonal antibodies (MAbs). Intravenous or intraperitoneal immunization of BALB/c mice with VSV-C/E1/E2 or VSVΔG-C/E1/E2 resulted in significant and surprisingly comparable HCV core or E2 antibody responses compared to those of control mice. In addition, both virus types generated HCV C-, E1-, or E2-specific gamma interferon (IFN-γ)-producing CD8+ T cells, as determined by enzyme-linked immunospot (ELISPOT) analysis. Mice immunized with VSVΔG-C/E1/E2 were also protected against the formation of tumors expressing HCV E2 (CT26-hghE2t) and exhibited CT26-hghE2t-specific IFN-γ-producing and E2-specific CD8+ T-cell activity. Finally, recombinant vaccinia virus (vvHCV.S) expressing the HCV structural proteins replicated at significantly lower levels when inoculated into mice immunized with VSV-C/E1/E2 or VSVΔG-C/E1/E2, but not with control viruses. Our data therefore illustrate that potentially safer replication-defective VSV can be successfully engineered to express high levels of antigenically authentic HCV glycoproteins. In addition, this strategy may therefore serve in effective vaccine and immunotherapy-based approaches to the treatment of HCV-related disease.

scholarly journals Prediction of Physicochemical Properties of SARS-CoV-2 Protein in Bangladesh

2020 ◽  
Author(s):  
Nilanjan Roy
Keyword(s):  
Physicochemical Properties ◽  
Development Process ◽  
Vaccine Development ◽  
Viral Proteins ◽  
Instability Index ◽  
Subunit Vaccines ◽  
Grand Average ◽  
Rapid Production ◽  
Aliphatic Index ◽  
Inactivated Vaccines

Awareness of the physicochemical properties of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is urgently required for the rapid production of live attenuated and inactivated vaccines. To develop subunit vaccines, it's also important to understand these properties for similar viral proteins. In this study, we predicted the physicochemical properties of SARS-CoV-2 protein that has been sequenced from Bangladeshi patients. Here we reported the number of amino acids, molecular weight, theoretical pI, amino acid composition, extinction coefficients, estimated half-life, instability index, aliphatic index, and grand average of hydropathicity of the SARS-CoV-2 protein in Bangladesh. As Bangladesh is consistently trying to contribute in the vaccine development process of SARS-CoV-2, we believe that this biocomputational study of physicochemical properties will give meaningful insights and will ease the way of vaccine development.

A Lethal Aerosol Exposure Model of Nipah Virus Strain Bangladesh in African Green Monkeys

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S431-S435 ◽  
Author(s):  
Abhishek N Prasad ◽  
Krystle N Agans ◽  
Satheesh K Sivasubramani ◽  
Joan B Geisbert ◽  
Viktoriya Borisevich ◽  
...  
Keyword(s):  
Nipah Virus ◽  
Case Fatality ◽  
Respiratory Illness ◽  
Health Concern ◽  
Exposure Model ◽  
Pathogenic Potential ◽  
Aerosol Model ◽  
Aerosol Exposure ◽  
Significant Public Health ◽  
Green Monkeys

Abstract The high case-fatality rates and potential for use as a biological weapon make Nipah virus (NiV) a significant public health concern. Previous studies assessing the pathogenic potential of NiV delivered by the aerosol route in African green monkeys (AGMs) used the Malaysia strain (NiVM), which has caused lower instances of respiratory illness and person-to-person transmission during human outbreaks than the Bangladesh strain (NiVB). Accordingly, we developed a small particle aerosol model of NiVB infection in AGMs. Consistent with other mucosal AGM models of NiVB infection, we achieved uniform lethality and disease pathogenesis reflective of that observed in humans.

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.

scholarly journals Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Muhammad Tahir ul Qamar ◽  
Farah Shahid ◽  
Sadia Aslam ◽  
Usman Ali Ashfaq ◽  
Sidra Aslam ◽  
...  
Keyword(s):  
In Silico ◽  
Subunit Vaccine ◽  
Human Leukocyte ◽  
Surface Glycoprotein ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Severe Illness ◽  
T Cell Epitopes ◽  
Hla Binding ◽  
K 12

Abstract Background Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. Methods Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. Results Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. Conclusion The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.

Identification of potential vaccine candidates against SARS-CoV-2, A step forward to fight COVID 19: A Reverse Vaccinology Approach (Preprint)

2021 ◽  
Author(s):  
Ekta Gupta ◽  
Rupesh Kumar Mishra ◽  
Ravi Ranjan Kumar Niraj
Keyword(s):  
Viral Disease ◽  
Surface Glycoprotein ◽  
Antigenic Peptide ◽  
Reverse Vaccinology ◽  
Effective Vaccine ◽  
Global Public Health ◽  
Health Crisis ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Potential Vaccine

UNSTRUCTURED The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The etiological agent of COVID-19, a recently arose disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, more research in the field of effecting vaccine against this emerged viral disease is indeed a need of the hour. In the current study, we collected SARS-CoV-2 genome which is prominent in India against human host, furthermore using reverse vaccinology here we prove effective vaccine candidates that can be milestone in the battle against COVID19. This novel study divulged one promising antigenic peptide GVYFASTEK from surface glycoprotein (protein accession no. - QIA98583.1) of SARS-CoV-2, which was predicted to be interacted with MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking and simulation studies were verified molecular interaction of this prime antigenic peptide with the residues of HLA-A*11-01 allele for MHC Class I. After vigorous analysis, this peptide was predicted to be a suitable epitope that is capable to induce a strong cell-mediated immune response against the SARS-CoV-2. Consequences from the current study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.

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