scholarly journals An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

2020 ◽  
Author(s):  
Md Anik Ashfaq Khan ◽  
Jenifar Quaiyum Ami ◽  
Khaledul Faisal ◽  
Rajashree Chowdhury ◽  
Prakash Ghosh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Leishmania Donovani ◽  
Methodological Approach ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Secretory Proteins ◽  
Binding Interaction ◽  
Binding Interface

Abstract Background Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of the human disease propagating form of Leishmania donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. Methods By using an immunoinformatic approach, CD4+ and CD8+ T cell-specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a Toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization. Results Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum , covering theoretically more than 98% of the global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response. Conclusions The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.

scholarly journals An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

2020 ◽  
Author(s):  
Md Anik Ashfaq Khan ◽  
Jenifar Quaiyum Ami ◽  
Khaledul Faisal ◽  
Rajashree Chowdhury ◽  
Prakash Ghosh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Leishmania Donovani ◽  
Methodological Approach ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Secretory Proteins ◽  
Binding Interaction ◽  
Binding Interface

Abstract Background: Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic fatal disease with high socio-economic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of human disease propagating form of L. donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. Methods: By using an immunoinformatic approach, CD4+ and CD8+ T cell specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization.Results: Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum- covering theoretically more than 98% of global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response.Conclusions: The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.

scholarly journals An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

2020 ◽  
Author(s):  
Md Anik Ashfaq Khan ◽  
Jenifar Quaiyum Ami ◽  
Khaledul Faisal ◽  
Rajashree Chowdhury ◽  
Prakash Ghosh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Leishmania Donovani ◽  
Methodological Approach ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Secretory Proteins ◽  
Binding Interaction ◽  
Binding Interface

Abstract Background Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic fatal disease with high socio-economic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of human disease propagating form of L. donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. Methods By using an immunoinformatic approach, CD4+ and CD8+ T-cell specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization. Results Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum - covering theoretically more than 98% of global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B- as well as CD4+ T-cell generation potential, and likely chance of a more Th1 polarized response. Conclusions The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.

scholarly journals An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

2019 ◽  
Author(s):  
Md Anik Ashfaq Khan ◽  
Jenifar Quaiyum Ami ◽  
Khaledul Faisal ◽  
Rajashree Chowdhury ◽  
Prakash Ghosh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Leishmania Donovani ◽  
Methodological Approach ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Secretory Proteins ◽  
Binding Interaction ◽  
Binding Interface

Abstract Background Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic fatal disease with high socio-economic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of human disease propagating form of L. donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates.Methods By using an immunoinformatic approach, CD4 and CD8 T-cell specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization.Results Selected epitopes from physiologically important L. donovani proeins were found mostly conserved in L. infantum - covering theoretically more than 98% of global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B- as well as CD4 T-cell generation potential, and likely chance of a more Th1 polarized response.Conclusions The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.

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 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 Rhipicephalus microplus lipocalins (LRMs): Genomic identification and analysis of the bovine immune response using in silico predicted B and T cell epitopes

2013 ◽  
Vol 43 (9) ◽  
pp. 739-752 ◽  
Author(s):  
Manuel Rodriguez-Valle ◽  
Paula Moolhuijzen ◽  
Emily K. Piper ◽  
Olivia Weiss ◽  
Megan Vance ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Rhipicephalus Microplus ◽  
T Cell Epitopes

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.

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