scholarly journals Prediction of CD8 and CD4 T cell epitopes in the polyprotein of Zika Virus; an immunoinformatics approach

2018 ◽  
Author(s):  
Tahreem Zaheer ◽  
Muhammad Talha Shahid Khan ◽  
Hamza Arshad Dar ◽  
Shifa Tariq Ashraf ◽  
Rehan Zafar Paracha ◽  
...  
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Viral Infections ◽  
Consensus Sequence ◽  
Experimental Studies ◽  
Cd4 T Cell ◽  
Binding Affinities ◽  
T Cell Epitopes ◽  
Vaccine Candidates ◽  
Global Threat

Background: Zika virus (ZIKV) is an arbovirus that belongs to family Flaviviridae. The virus has emerged as a global threat and no FDA approved vaccine is available, so an efficient vaccine needs to be designed in order to prevent the infection. Computationally designed vaccines can be used for broad-spectrum therapeutics as they can evoke response against viral infections. In the current study, we have predicted antigenic promiscuous T cell epitopes from Zika virus polyprotein using a range of immune-informatics tools and servers. Methods: A total of 238 polyprotein sequences derived from 238 complete genomes were retrieved using NIAID Virus Pathogen Resource and multiple aligned. Using a consensus sequence, the promiscuous CD8-T cell epitopes were predicted from Propred I and CTLPred and their binding affinities were determined by NetMHC4.0. CD4-T cell epitopes were predicted using ProPred and the binding affinities were determined by MHCPred. Antigenicity score and Immunogenicity score was determined from Vaxijen 2.0 and IEDB immunogenicity tool. Homology was found by pBLAST. Results: Among 78 predicted HLA-I binding epitopes, 19 highly antigenic, immunogenic and high-affinity epitopes are prioritized among which 15 are novel vaccine candidates. However, 66 strong HLA-II interacting T cell epitopes are pooled out from 70 predicted epitopes. Among the shortlisted CD4-T cell epitopes 56 epitopes are novel. Conclusion: Epitope-based vaccines are robust and promising candidates against bacterial and viral infections. The predicted epitopes can serve as potential vaccine candidates. Our study shows promising epitopes that can be used to generate stimulate active immune responses in the majority of the human population around the world, However, our results need validation through experimental studies for confirmation.

scholarly journals Prediction of CD8 and CD4 T cell epitopes in the polyprotein of Zika Virus; an immunoinformatics approach

2018 ◽  
Author(s):  
Tahreem Zaheer ◽  
Muhammad Talha Shahid Khan ◽  
Hamza Arshad Dar ◽  
Shifa Tariq Ashraf ◽  
Rehan Zafar Paracha ◽  
...  
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Viral Infections ◽  
Consensus Sequence ◽  
Experimental Studies ◽  
Cd4 T Cell ◽  
Binding Affinities ◽  
T Cell Epitopes ◽  
Vaccine Candidates ◽  
Global Threat

Background: Zika virus (ZIKV) is an arbovirus that belongs to family Flaviviridae. The virus has emerged as a global threat and no FDA approved vaccine is available, so an efficient vaccine needs to be designed in order to prevent the infection. Computationally designed vaccines can be used for broad-spectrum therapeutics as they can evoke response against viral infections. In the current study, we have predicted antigenic promiscuous T cell epitopes from Zika virus polyprotein using a range of immune-informatics tools and servers. Methods: A total of 238 polyprotein sequences derived from 238 complete genomes were retrieved using NIAID Virus Pathogen Resource and multiple aligned. Using a consensus sequence, the promiscuous CD8-T cell epitopes were predicted from Propred I and CTLPred and their binding affinities were determined by NetMHC4.0. CD4-T cell epitopes were predicted using ProPred and the binding affinities were determined by MHCPred. Antigenicity score and Immunogenicity score was determined from Vaxijen 2.0 and IEDB immunogenicity tool. Homology was found by pBLAST. Results: Among 78 predicted HLA-I binding epitopes, 19 highly antigenic, immunogenic and high-affinity epitopes are prioritized among which 15 are novel vaccine candidates. However, 66 strong HLA-II interacting T cell epitopes are pooled out from 70 predicted epitopes. Among the shortlisted CD4-T cell epitopes 56 epitopes are novel. Conclusion: Epitope-based vaccines are robust and promising candidates against bacterial and viral infections. The predicted epitopes can serve as potential vaccine candidates. Our study shows promising epitopes that can be used to generate stimulate active immune responses in the majority of the human population around the world, However, our results need validation through experimental studies for confirmation.

scholarly journals Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection

2018 ◽  
Vol 9 ◽  
Author(s):  
Maximilian Koblischke ◽  
Karin Stiasny ◽  
Stephan W. Aberle ◽  
Stefan Malafa ◽  
Georgios Tsouchnikas ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Zika Virus ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Zika Virus Infection ◽  
Structural Influence

scholarly journals T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

2017 ◽  
Vol 2 (2) ◽  
pp. 274 ◽  
Author(s):  
Dominic Paquin-Proulx ◽  
Fabio E. Leal ◽  
Cassia G. Terrassani Silveira ◽  
Alvino Maestri ◽  
Claudia Brockmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Cell Epitope ◽  
Denv Infection ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection.Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT.Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects.Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

scholarly journals Corrigendum: Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection

2018 ◽  
Vol 9 ◽  
Author(s):  
Maximilian Koblischke ◽  
Karin Stiasny ◽  
Stephan W. Aberle ◽  
Stefan Malafa ◽  
Georgios Tsouchnikas ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Zika Virus ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Zika Virus Infection ◽  
Structural Influence

scholarly journals T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

2017 ◽  
Vol 2 (2) ◽  
pp. 274
Author(s):  
Dominic Paquin-Proulx ◽  
Fabio E. Leal ◽  
Cassia G. Terrassani Silveira ◽  
Alvino Maestri ◽  
Claudia Brockmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Cell Epitope ◽  
Denv Infection ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection.Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT.Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects.Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

Prediction of Prophylactic Peptide Vaccine Candidates for Human Papillomavirus (HPV): An Immunoinformatics and Reverse Vaccinology Approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Mehreen Ismail ◽  
Zureesha Sajid ◽  
Amjad Ali ◽  
Xiaogang Wu ◽  
Syed Aun Muhammad ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Binding Affinity ◽  
Cd8 T Cells ◽  
Reverse Vaccinology ◽  
Host Immune System ◽  
T Cell Epitopes ◽  
Multiple Alleles ◽  
Vaccine Candidates

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, Tcell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

Immuno-informatics-based identification of novel potential B cell and T cell epitopes to fight Zika virus infections

2020 ◽  
Vol 20 ◽  
Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Zika Virus ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Virus Infections ◽  
Histocompatibility Complex

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.

Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

2005 ◽  
Vol 62 (1) ◽  
pp. 77-86 ◽  
Author(s):  
M. -D. Nastke† ◽  
L. Herrgen† ◽  
S. Walter ◽  
D. Wernet ◽  
H. -G. Rammensee ◽  
...  
Keyword(s):  
T Cell ◽  
Human Cytomegalovirus ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire
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