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Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development
Hepatitis C is an inflammatory infectious disease of the liver caused by the Hepatitis C Virus (HCV). It is a global pandemic, chronically inflicting 150 million people worldwide, with millions of new infections arising annually. The standard therapy of HCV is expensive, associated with severe side...
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2014
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| _version_ | 1867613416311488512 |
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| access_status_str | Open Access |
| author | Abdel-Hady, Karim Mohamed Ali |
| author_browse | Abdel-Hady, Karim Mohamed Ali |
| author_facet | Abdel-Hady, Karim Mohamed Ali |
| author_sort | Abdel-Hady, Karim Mohamed Ali |
| collection | Thesis |
| dc_rights_str_mv | The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. |
| description | Hepatitis C is an inflammatory infectious disease of the liver caused by the Hepatitis C Virus (HCV). It is a global pandemic, chronically inflicting 150 million people worldwide, with millions of new infections arising annually. The standard therapy of HCV is expensive, associated with severe side effects, and has variable success rates. Thus far, no HCV vaccine has been developed, owing to the challenges that faced and still face its development. Despite these challenges, several attempts have been taken to develop a vaccine, some of which have progressed to phase II clinical trials. Most of these attempts, however, have focused on HCV genotypes 1 and 2 as vaccine targets, and almost no attention has been given to HCV genotype 4 (HCV-4), the viral genotype most prevalent in the Middle East and Central Africa. In an attempt to fill this gap in HCV-4 vaccine research, this project describes the in silico identification of a group of highly conserved and immunogenic T-cell epitopes from the HCV-4 proteome, using the iVAX immunoinformatics toolkit (EpiVax Inc., RI, USA), as a first step towards the development of an epitope-driven vaccine against the viral genotype. Furthermore, it puts forth a fast and inexpensive method for the validation of the results retrospectively using the repository of empirical HCV immune epitope data on the Immune Epitope Database (IEDB). 90 HLA class I and 14 HLA class II epitopes were identified. From those, 20 HLA class I epitopes were found to be previously uncharacterized, while the in silico HLA binding predictions for 27 others (class I and class II) have been retrospectively validated. The retrospective validation results for 4 of the identified HLA class II epitopes were confirmed by a pilot HLA class II binding assay. Furthermore, an investigation of the conservancy of a selected set of the identified epitopes in newly re-sequenced HCV strains from the Egyptian population was performed. The identified and retrospectively validated set of epitopes constitutes a good target for further immunogenicity testing and epitope-driven vaccine development against HCV-4. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-2171 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:47.730Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-2171 Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development Abdel-Hady, Karim Mohamed Ali Hepatitis C is an inflammatory infectious disease of the liver caused by the Hepatitis C Virus (HCV). It is a global pandemic, chronically inflicting 150 million people worldwide, with millions of new infections arising annually. The standard therapy of HCV is expensive, associated with severe side effects, and has variable success rates. Thus far, no HCV vaccine has been developed, owing to the challenges that faced and still face its development. Despite these challenges, several attempts have been taken to develop a vaccine, some of which have progressed to phase II clinical trials. Most of these attempts, however, have focused on HCV genotypes 1 and 2 as vaccine targets, and almost no attention has been given to HCV genotype 4 (HCV-4), the viral genotype most prevalent in the Middle East and Central Africa. In an attempt to fill this gap in HCV-4 vaccine research, this project describes the in silico identification of a group of highly conserved and immunogenic T-cell epitopes from the HCV-4 proteome, using the iVAX immunoinformatics toolkit (EpiVax Inc., RI, USA), as a first step towards the development of an epitope-driven vaccine against the viral genotype. Furthermore, it puts forth a fast and inexpensive method for the validation of the results retrospectively using the repository of empirical HCV immune epitope data on the Immune Epitope Database (IEDB). 90 HLA class I and 14 HLA class II epitopes were identified. From those, 20 HLA class I epitopes were found to be previously uncharacterized, while the in silico HLA binding predictions for 27 others (class I and class II) have been retrospectively validated. The retrospective validation results for 4 of the identified HLA class II epitopes were confirmed by a pilot HLA class II binding assay. Furthermore, an investigation of the conservancy of a selected set of the identified epitopes in newly re-sequenced HCV strains from the Egyptian population was performed. The identified and retrospectively validated set of epitopes constitutes a good target for further immunogenicity testing and epitope-driven vaccine development against HCV-4. 2014-02-01T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/1172 https://fount.aucegypt.edu/context/etds/article/2171/viewcontent/Karim_20Abdel_Hady_MSc._20Thesis.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain Hepatitis C virus Immunoinformatics |
| spellingShingle | Hepatitis C virus Immunoinformatics Abdel-Hady, Karim Mohamed Ali Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title | Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title_full | Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title_fullStr | Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title_full_unstemmed | Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title_short | Identification of T-cell epitopes in the Hepatitis C virus genotype 4 proteome: a step towards epitope-driven vaccine development |
| title_sort | identification of t cell epitopes in the hepatitis c virus genotype 4 proteome a step towards epitope driven vaccine development |
| topic | Hepatitis C virus Immunoinformatics |
| url | https://fount.aucegypt.edu/etds/1172 https://fount.aucegypt.edu/context/etds/article/2171/viewcontent/Karim_20Abdel_Hady_MSc._20Thesis.pdf |
| work_keys_str_mv | AT abdelhadykarimmohamedali identificationoftcellepitopesinthehepatitiscvirusgenotype4proteomeasteptowardsepitopedrivenvaccinedevelopment |