scholarly journals In-silico Design of Multi-epitope Vaccine against Nipah Virus using Immunoinformatics Approach

2021 ◽  
Vol 15 (1) ◽  
pp. 212-231
Author(s):  
Suraj Raju ◽  
Debasish Sahoo ◽  
Vikas Kumar Bhari
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Vaccine Development ◽  
Homology Modelling ◽  
Nipah Virus ◽  
Docking Simulation ◽  
Dynamics Simulation ◽  
Cytotoxic T Cell ◽  
Viral Spread

Nipah virus is a pleomorphic virus that causes high mortality with unpredictable outbreaks. The virus also shows high zoonotic potential with long term neurological damage after recovery further adding to the disease burden. An in-silico epitope-based vaccine offers a promising solution to supplement wider efforts to control the viral spread. This is achieved through immunoinformatics approach using a plethora of servers available. We derived cytotoxic T-cell, T-Helper, B-cell and IFN-γ targeting epitopes from surface glycoprotein G. Cytotoxic T-cell specific epitopes, HLA-B*4402, chimeric multiepitope vaccine structures were prepared using homology modelling method. The structures were validated using various methods and docking simulation was performed between epitopes and HLA-B*4402. Similarly, the vaccine construct was docked to Toll like receptor-4 and a molecular dynamics simulation was performed to assess stability of interaction. Both the docking simulations showed stable interactions with their respective receptors. Immune-simulation was carried out to validate the efficacy of vaccine candidate which showed elevated levels of antibodies such as IgM and IgG due to increase in active B cell population. Both in-vitro and in-vivo serological analysis is required for confirmation of vaccine potency. To facilitate this effort, codon optimization was undertaken to remove existing codon bias. The optimized gene sequence was cloned into the PUC19 vector to express in Escherichia coli K12 strain. Additionally, a poly histidine (6xHis) tag was added at the C-terminal end to ease the purification step. The immune-informatics approach hopes to accelerate vaccine development process to reduce the risk of attenuation while increasing the success rates of pre-clinical trials.

scholarly journals Immuno-informatics approach for multi-epitope vaccine designing against SARS-CoV-2

2020 ◽  
Author(s):  
Souvik Banerjee ◽  
Kaustav Majumder ◽  
Gerardo Jose Gutierrez ◽  
Debkishore Gupta ◽  
Bharti Mittal
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Dynamics Simulation ◽  
Cytotoxic T Cell ◽  
Epitope Vaccine ◽  
B Cell Epitopes ◽  
Corona Virus ◽  
The World

AbstractThe novel Corona Virus Disease 2019 (COVID-19) pandemic has set the fatality rates ablaze across the world. So, to combat this disease, we have designed a multi-epitope vaccine from various proteins of Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2) with an immuno-informatics approach, validated in silico to be stable, non-allergic and antigenic. Cytotoxic T-cell, helper T-cell, and B-cell epitopes were computationally predicted from six conserved protein sequences among four viral strains isolated across the world. The T-cell epitopes, overlapping with the B-cell epitopes, were included in the vaccine construct to assure the humoral and cell-mediated immune response. The beta-subunit of cholera toxin was added as an adjuvant at the N-terminal of the construct to increase immunogenicity. Interferon-gamma inducing epitopes were even predicted in the vaccine. Molecular docking and binding energetics studies revealed strong interactions of the vaccine with immune-stimulatory toll-like receptors (TLR) −2, 3, 4. Molecular dynamics simulation of the vaccine ensured in vivo stability in the biological system. The immune simulation of vaccine evinced elevated immune response. The efficient translation of the vaccine in an expression vector was assured utilizing in silico cloning approach. Certainly, such a vaccine construct could reliably be effective against COVID-19.

scholarly journals Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thabile Madlala ◽  
Victoria T. Adeleke ◽  
Abiodun J. Fatoba ◽  
Moses Okpeku ◽  
Adebayo A. Adeniyi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Docking Simulation ◽  
Cost Effective ◽  
Economic Loss ◽  
T Cell Epitopes ◽  
Live Vaccines ◽  
Physiochemical Parameters

AbstractDrug resistance against coccidiosis has posed a significant threat to chicken welfare and productivity worldwide, putting daunting pressure on the poultry industry to reduce the use of chemoprophylactic drugs and live vaccines in poultry to treat intestinal diseases. Chicken coccidiosis, caused by an apicomplexan parasite of Eimeria spp., is a significant challenge worldwide. Due to the experience of economic loss in production and prevention of the disease, development of cost-effective vaccines or drugs that can stimulate defence against multiple Eimeria species is imperative to control coccidiosis. This study explored Eimeria immune mapped protein-1 (IMP-1) to develop a multiepitope-based vaccine against coccidiosis by identifying antigenic T-cell and B-cell epitope candidates through immunoinformatic techniques. This resulted in the design of 7 CD8+, 21 CD4+ T-cell epitopes and 6 B-cell epitopes, connected using AAY, GPGPG and KK linkers to form a vaccine construct. A Cholera Toxin B (CTB) adjuvant was attached to the N-terminal of the multiepitope construct to improve the immunogenicity of the vaccine. The designed vaccine was assessed for immunogenicity (8.59968), allergenicity and physiochemical parameters, which revealed the construct molecular weight of 73.25 kDa, theoretical pI of 8.23 and instability index of 33.40. Molecular docking simulation of vaccine with TLR-5 with binding affinity of − 151.893 kcal/mol revealed good structural interaction and stability of protein structure of vaccine construct. The designed vaccine predicts the induction of immunity and boosted host's immune system through production of antibodies and cytokines, vital in hindering surface entry of parasites into host. This is a very important step in vaccine development though further experimental study is still required to validate these results.

scholarly journals Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Onyeka S. Chukwudozie ◽  
Rebecca C. Chukwuanukwu ◽  
Onyekachi O. Iroanya ◽  
Daniel M. Eze ◽  
Vincent C. Duru ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Rna Binding ◽  
Peptide Vaccine ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Effective Vaccine ◽  
Translation Efficiency ◽  
T Cell Epitopes

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

scholarly journals In silico Vaccine Design against Dengue Virus Type 2 Envelope Glycoprotein

2020 ◽  
Vol 27 (3) ◽  
pp. 228
Author(s):  
Muhammad Adnan ◽  
Matin Nuhamunada ◽  
Lisna Hidayati ◽  
Nastiti Wijayanti
Keyword(s):  
T Cell ◽  
B Cell ◽  
Envelope Glycoprotein ◽  
In Silico ◽  
Vaccine Development ◽  
Severe Infection ◽  
Cell Types ◽  
Peptide Region ◽  
Dengue Virus Type 2

Dengue fever is caused by the mosquito-borne virus termed (DENV). However, DENV-2 has been identified as the most prevalent amongst the Indonesian pediatric urban population, in contrast with the other four serotypes. Therefore, it is important to reduce severe infection risk by adopting preventive measures, including through vaccine development. The aim of this study, therefore is to use various in silico tools in the design of epitope-based peptide vaccines (T-cell and B-cell types), based on the DENV-2 envelope glycoprotein sequences available. Therefore, in silico methods were adopted in the analysis of the retrieved protein sequences. This technique was required to determine the most immunogenic protein, and is achieved through conservancy analysis, epitope identification, molecular simulation, and allergenicity assessment. Furthermore, B4XPM1, and KAWLVHRQW were identified from positions 204-212, while the 77 to 85 peptide region was considered the most potent T-cell and B-cell epitopes. The interaction between KAWLVHRQW and HLA-C*12:03 occurs with maximum population coverage, alongside high conservancy (96.98%) and binding affinity. These results indicated a potential for the designed epitopes to demonstrate high immunity against DENV-2.

scholarly journals Prediction of Epitope-Based Peptides for the Utility of Vaccine Development from Fusion and Glycoprotein of Nipah Virus Using In Silico Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
M. Sadman Sakib ◽  
Md. Rezaul Islam ◽  
A. K. M. Mahbub Hasan ◽  
A. H. M. Nurun Nabi
Keyword(s):  
B Cell ◽  
In Silico ◽  
Vaccine Development ◽  
Nipah Virus ◽  
Cell Epitope ◽  
Class Ii ◽  
Host Cells ◽  
Class I ◽  
Cell Mediated Immunity ◽  
Population Coverage

This study aims to design epitope-based peptides for the utility of vaccine development by targeting glycoprotein G and envelope protein F of Nipah virus (NiV) that, respectively, facilitate attachment and fusion of NiV with host cells. Using various databases and tools, immune parameters of conserved sequence(s) from G and F proteins of different isolates of NiV were tested to predict probable epitope(s). Binding analyses of the peptides with MHC class-I and class-II molecules, epitope conservancy, population coverage, and linear B cell epitope prediction were analyzed. Predicted peptides interacted with seven or more MHC alleles and illustrated population coverage of more than 99% and 95%, for G and F proteins, respectively. The predicted class-I nonamers, SLIDTSSTI and EWISIVPNF, superimposed on the putative decameric B cell epitopes, were also identified as core sequences of the most probable class-II 15-mer peptides GPKVSLIDTSSTITI and EWISIVPNFILVRNT. These peptides were further validated for their binding to specific HLA alleles using in silico docking technique. Our in silico analysis suggested that the predicted epitopes, either GPKVSLIDTSSTITI or EWISIVPNFILVRNT, could be a better choice as universal vaccine component against NiV irrespective of different isolates which may elicit both humoral and cell-mediated immunity.

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.

In silico prediction of T‐cell and B‐cell epitopes of human papillomavirus type 16 L1 protein

2021 ◽  
Author(s):  
Shahab Mahmoudvand ◽  
Somayeh Shokri ◽  
Manoochehr Makvandi ◽  
Reza Taherkhani ◽  
Mohammad Rashno ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
In Silico Prediction ◽  
B Cell Epitopes ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

scholarly journals Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam K. Wheatley ◽  
Jennifer A. Juno ◽  
Jing J. Wang ◽  
Kevin J. Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Natural Infection ◽  
Population Level ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Specific Igg ◽  
Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions

2021 ◽  
pp. 106002802098841
Author(s):  
Zachery Halford ◽  
Carli Coalter ◽  
Vanessa Gresham ◽  
Tabitha Brown
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Phase Iii ◽  
Cytotoxic T Cell ◽  
Bispecific T Cell Engager

Objective: To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL). Data Sources: We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: blinatumomab, Blincyto, lymphoblastic leukemia, and bispecific T-cell engager. Study Selection and Data Extraction: All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion. Data Synthesis: Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively. Relevance to Patient Care and Clinical Practice: Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in “chemotherapy-free” combination regimens. Conclusions: Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.

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