scholarly journals INDENTIFYING FUNCTIONALLY CONSERVED REGIONS AND PREDICTING T-CELL EPITOPES ON PROTEINS OF INFLUENZA A VIRUS

2009 ◽  
Vol 12 (9) ◽  
pp. 38-46
Author(s):  
Van Hai Van ◽  
Thuy Thi Thanh Le ◽  
Phuong Thi Ngoc Cao ◽  
Bich Thi Vu ◽  
Thuoc Linh Tran
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
T Cell Epitopes ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Universal Vaccine ◽  
Conserved Regions

Influenza A viruses are of worldwide concerns because of their rapidly and endlessly genetic changes. Based on the experimental influenza A virus databases, we analyzed conserved regions on the protein sequences of influenza A virus to facilitate the design of universal vaccine and the prediction of changing tendency of influenza A viral strains. Our study was carried out on eleven viral functional proteins: HA, NA, PA, NSI, NS2, MI, M2, NP, PBI, PB1_F2 and PB2. From these groups, the clusters were formed on subtypes, hosts, countries and years of collection, followed by multiple sequence alignments by two tools ClustalW and MAFFT. Conserved sequences of 9 amino acid residues were selected and used for T-cell epitope prediction by SEP (System for Epitope Prediction). In addition, we also predicted the function of these conserved regions using information on function of influenza A viral proteins from the Swissprot database.

scholarly journals Why Are CD8 T Cell Epitopes of Human Influenza A Virus Conserved?

2018 ◽  
Author(s):  
Zheng-Rong Tiger Li ◽  
Veronika I. Zarnitsyna ◽  
Anice C. Lowen ◽  
Daniel Weissman ◽  
Katia Koelle ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cd8 T Cell ◽  
Influenza Vaccines ◽  
T Cell Epitopes ◽  
Word Count ◽  
Mhc I ◽  
Escape Variant ◽  
Replicative Fitness

AbstractThe high-degree conservation of CD8 T cell epitopes of influenza A virus (IAV) may allow T cell-inducing vaccines effective across different strains and subtypes. This conservation is not fully explained by functional constraint, since additional mutation(s) can compensate the replicative fitness loss of IAV escape-variant. Here, we propose three additional mechanisms that contribute to the conservation of CD8 T cell epitopes of IAV. First, influenza-specific CD8 T cells may protect predominantly against severe pathology rather than infection and may only have a modest effect on transmission. Second, polymorphism of human MHC-I gene restricts the advantage of an escape-variant to only a small fraction of human population, who carry the relevant MHC-I alleles. Finally, infection with CD8 T cell-escapevariants may result in compensatory increase in the responses to other epitopes of IAV. A combination of population genetics and epidemiological models is used to examine how the interplay between these mechanisms affects the rate of invasion of IAV escape-variants. We conclude that the invasion of an escape-variant will be very slow with a timescale of decades or longer, even if the escape-variant does not have a replicative fitness loss. Our results suggest T cell-inducing vaccines may not engender the rapid evolution of IAV and serve as a foundation for future modeling works on the long-term effectiveness and impacts of T cell-inducing influenza vaccines. (Word count: 221)ImportanceUniversal influenza vaccines against the conserved epitopes of influenza A virus have been proposed to minimize the burden of seasonal outbreaks and prepare for the pandemics. However, it is not clear to which extent the T cell-inducing vaccines will select for viruses that escape the T cell responses. Our mathematical models suggest how the nature of CD8 T cell protection contributes to the conservation of the CD8 T cell epitopes of influenza A virus. Also, it points out the essential biological parameters and questions that need addressing by future experimental works. (Word count: 91)

scholarly journals Immunoinformatics Approach Identified Two Highly Conserved B and T Cell Epitopes, LEASKRWAF and DSPLEASKRWAFRTG, for Effective Vaccine Design against Ebola and Marburg Viruses

2019 ◽  
pp. 1-16
Author(s):  
Md. Shahadat Hossain ◽  
Hasan Al. Reza ◽  
Mohammad Shahnoor Hossain
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Simulation Analysis ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Docking Simulation ◽  
Hemorrhagic Fever ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Mhc Molecules

Aims: Ebola and Marburg viruses cause fatal hemorrhagic fever in both human and non-human primates. Absence of any licensed vaccine has further deteriorated the problem. In the present study, we aimed to design potential epitope based vaccines against these viruses using computational approaches. Methodology: By using various bioinformatics tools and databases, we analyzed the conserved glycoprotein sequences of Ebola and Marburg viruses and predicted two potential epitopes which may be used as peptide vaccines. Results: Using various B-cell and T-cell epitope prediction servers, four highly conserved epitopes were identified. Epitope conservancy analysis showed that  “LEASKRWAF” and “DSPLEASKRWAFRTG” epitopes were 100% and 93.62% conserved and the worldwide population coverage of “LEASKRWAF” interacting with MHC class I molecules and “DSPLEASKRWAFRTG” interacting with MHC class II molecules were 78.74% and 75.75% respectively. Immunoinformatics analysis showed that they are highly immunogenic, flexible and accessible to antibody. Molecular docking simulation analysis demonstrated a very significant interaction between epitopes and MHC molecules with lower binding energy. Cytotoxic analysis and ADMET test also supported their potential as vaccine candidates. Conclusion: In sum, our in silico approach demonstrated that both “LEASKRWAF” and “DSPLEASKRWAFRTG” hold the promise for the development of common vaccine against Ebola and Marburg viruses.

scholarly journals Prediction of T and B Cell Epitopes in the Proteome of SARS-CoV-2 for Potential Use in Diagnostics and Vaccine Design

2020 ◽  
Author(s):  
Parvez Slathia ◽  
Preeti Sharma,
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Vaccine Design ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
The People ◽  
Skilled Manpower ◽  
Prophylactic Measures

<p>The world is currently battling the Covid-19 pandemic for which there is no therapy available. Prophylactic measures like vaccines can effectively thwart the disease burden. The current methods of detection are PCR based and require skilled manpower to operate. The availability of cheap and ready to use diagnostics like serological methods can ease the detection of SARS-CoV-2 virus. In the current study, immunoinformatics tools have been used to predict T and B cell epitopes present in all the proteins of this virus. NetMHCPan, NetCTL and NetMHCII servers were used for T cell epitope prediction while BepiPred and ABCPred were used for B cell epitope prediction. Population coverage analysis for T cell epitopes revealed that these could provide protection to the people throughout world. The T cell epitopes can exclusively used for vaccine design whereas B cell epitopes can be used for both vaccine design and developing diagnostic kits. </p> <p> </p>

scholarly journals Prediction of T and B Cell Epitopes in the Proteome of SARS-CoV-2 for Potential Use in Diagnostics and Vaccine Design

2020 ◽  
Author(s):  
Parvez Slathia ◽  
Preeti Sharma,
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Vaccine Design ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
The People ◽  
Skilled Manpower ◽  
Prophylactic Measures

<p>The world is currently battling the Covid-19 pandemic for which there is no therapy available. Prophylactic measures like vaccines can effectively thwart the disease burden. The current methods of detection are PCR based and require skilled manpower to operate. The availability of cheap and ready to use diagnostics like serological methods can ease the detection of SARS-CoV-2 virus. In the current study, immunoinformatics tools have been used to predict T and B cell epitopes present in all the proteins of this virus. NetMHCPan, NetCTL and NetMHCII servers were used for T cell epitope prediction while BepiPred and ABCPred were used for B cell epitope prediction. Population coverage analysis for T cell epitopes revealed that these could provide protection to the people throughout world. The T cell epitopes can exclusively used for vaccine design whereas B cell epitopes can be used for both vaccine design and developing diagnostic kits. </p> <p> </p>

scholarly journals Immune Tolerance-Adjusted Personalized Immunogenicity Prediction for Pompe Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne S. De Groot ◽  
Ankit K. Desai ◽  
Sandra Lelias ◽  
S. M. Shahjahan Miah ◽  
Frances E. Terry ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcomes ◽  
Pompe Disease ◽  
Clinical Decision Making ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
T Cell Epitopes ◽  
Enzyme Replacement ◽  
Hla Dr

Infantile-onset Pompe disease (IOPD) is a glycogen storage disease caused by a deficiency of acid alpha-glucosidase (GAA). Treatment with recombinant human GAA (rhGAA, alglucosidase alfa) enzyme replacement therapy (ERT) significantly improves clinical outcomes; however, many IOPD children treated with rhGAA develop anti-drug antibodies (ADA) that render the therapy ineffective. Antibodies to rhGAA are driven by T cell responses to sequences in rhGAA that differ from the individuals’ native GAA (nGAA). The goal of this study was to develop a tool for personalized immunogenicity risk assessment (PIMA) that quantifies T cell epitopes that differ between nGAA and rhGAA using information about an individual’s native GAA gene and their HLA DR haplotype, and to use this information to predict the risk of developing ADA. Four versions of PIMA have been developed. They use EpiMatrix, a computational tool for T cell epitope identification, combined with an HLA-restricted epitope-specific scoring feature (iTEM), to assess ADA risk. One version of PIMA also integrates JanusMatrix, a Treg epitope prediction tool to identify putative immunomodulatory (regulatory) T cell epitopes in self-proteins. Using the JanusMatrix-adjusted version of PIMA in a logistic regression model with data from 48 cross-reactive immunological material (CRIM)-positive IOPD subjects, those with scores greater than 10 were 4-fold more likely to develop ADA (p&lt;0.03) than those that had scores less than 10. We also confirmed the hypothesis that some GAA epitopes are immunomodulatory. Twenty-one epitopes were tested, of which four were determined to have an immunomodulatory effect on T effector response in vitro. The implementation of PIMA V3J on a secure-access website would allow clinicians to input the individual HLA DR haplotype of their IOPD patient and the GAA pathogenic variants associated with each GAA allele to calculate the patient’s relative risk of developing ADA, enhancing clinical decision-making prior to initiating treatment with ERT. A better understanding of immunogenicity risk will allow the implementation of targeted immunomodulatory approaches in ERT-naïve settings, especially in CRIM-positive patients, which may in turn improve the overall clinical outcomes by minimizing the development of ADA. The PIMA approach may also be useful for other types of enzyme or factor replacement therapies.

scholarly journals Reply to “Nuclear Export Signal and Immunodominant CD8+T Cell Epitope in Influenza A Virus Matrix Protein 1”

2012 ◽  
Vol 86 (18) ◽  
pp. 10259-10260
Author(s):  
Shuai Cao ◽  
Yi Shi ◽  
Shuguang Tan ◽  
Hao Song ◽  
George F. Gao ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Nuclear Export ◽  
Influenza A ◽  
Matrix Protein ◽  
Nuclear Export Signal ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Export Signal

scholarly journals Ab and T cell epitopes of influenza A virus, knowledge and opportunities

2007 ◽  
Vol 104 (1) ◽  
pp. 246-251 ◽  
Author(s):  
H.-H. Bui ◽  
B. Peters ◽  
E. Assarsson ◽  
I. Mbawuike ◽  
A. Sette
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Epitopes

scholarly journals EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Magdalena Molero-Abraham ◽  
John-Paul Glutting ◽  
Darren R. Flower ◽  
Esther M. Lafuente ◽  
Pedro A. Reche
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Variola Virus ◽  
T Cell Epitopes ◽  
Membrane Structures ◽  
Class Ii Mhc ◽  
Vaccinia Viruses ◽  
Virus Genomes

Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes.

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