scholarly journals Selection of Conserved Epitopes from Hepatitis C Virus for Pan-Populational Stimulation of T-Cell Responses

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Magdalena Molero-Abraham ◽  
Esther M. Lafuente ◽  
Darren R. Flower ◽  
Pedro A. Reche
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Natural Infection ◽  
Effective Means ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Selection Of

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server.

Magnitude of CD8+T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection

2009 ◽  
Vol 39 (3) ◽  
pp. 256-265 ◽  
Author(s):  
Hiroyoshi Doi ◽  
Kazumasa Hiroishi ◽  
Tomoe Shimazaki ◽  
Junichi Eguchi ◽  
Toshiyuki Baba ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Virus Infection ◽  
Acute Hepatitis ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Acute Hepatitis C ◽  
Hepatitis C Virus Infection ◽  
Cell Responses

PS-030-Cure of hepatitis C virus has limited impact on the functional and mitochondrial impairment of HCV-specific CD8+ T-cell responses

2019 ◽  
Vol 70 (1) ◽  
pp. e22
Author(s):  
Amare Aregay ◽  
Solomon Owusu Sekyere ◽  
Katja Deterdig ◽  
Kerstin Port ◽  
Julia Dietz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Limited Impact ◽  
Cell Responses ◽  
Mitochondrial Impairment

scholarly journals The Kinetics of Hepatitis C Virus-Specific CD8 T-Cell Responses in the Blood Mirror Those in the Liver in Acute Hepatitis C Virus Infection

2008 ◽  
Vol 82 (19) ◽  
pp. 9782-9788 ◽  
Author(s):  
Eui-Cheol Shin ◽  
Stefania Capone ◽  
Riccardo Cortese ◽  
Stefano Colloca ◽  
Alfredo Nicosia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Activity ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Functional Markers ◽  
Acute Hepatitis C ◽  
Cell Responses ◽  
Acute Hcv

ABSTRACT Peripheral blood T-cell responses are used as biomarkers in hepatitis C virus (HCV) vaccine trials. However, it is not clear how T-cell responses in the blood correlate with those in the liver, the infection site. By studying serial liver and blood samples of five vaccinated and five mock-vaccinated control chimpanzees during acute HCV infection, we demonstrate a correlation between HCV-specific CD8 T-cell responses in the blood and molecular and functional markers of T-cell responses in the liver. Thus, HCV-specific CD8 T-cell responses in the blood are valid markers for intrahepatic T-cell activity.

scholarly journals Differences in Hepatitis C Virus (HCV)-Specific CD8 T-Cell Phenotype during Pegylated Alpha Interferon and Ribavirin Treatment Are Related to Response to Antiviral Therapy in Patients Chronically Infected with HCV

2008 ◽  
Vol 82 (15) ◽  
pp. 7567-7577 ◽  
Author(s):  
Joana Caetano ◽  
António Martinho ◽  
Artur Paiva ◽  
Beatriz Pais ◽  
Cristina Valente ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Alpha Interferon ◽  
Response To Treatment ◽  
Cell Responses

ABSTRACT CD8 T cells play a major role in antiviral immune responses. Their importance for progression to chronic hepatitis C and response to treatment are still unclear. To address these issues, hepatitis C virus (HCV)-specific CD8 T-cell responses were monitored, at the single-cell level, using HLA class I pentamers specific for HCV core and HCV NS3 epitopes, in 23 chronically infected patients during treatment with pegylated alpha interferon and ribavirin. Patients who presented a sustained-response to therapy had stronger HCV-specific CD8 T-cell responses at all time points studied. Moreover, there were clear differences in the phenotypes of these cells during therapy: in responder patients, terminally differentiated effector cells increased more rapidly, and their frequency was always higher than in nonresponder patients. Sustained-responder patients also showed a higher frequency of HCV-specific CD8 T cells producing cytotoxic factors. Overall, a late and inefficient differentiation process of HCV-specific CD8 T cells might be associated with lack of response to treatment. A better knowledge of the mechanisms underlying this impairment may be important for the development of new therapeutic strategies to maintain, restore, or increase CD8 T-cell effectiveness in chronic HCV infection.

Monocytes transduced with lentiviral vectors expressing hepatitis C virus non-structural proteins and differentiated into dendritic cells stimulate multi-antigenic CD8+ T cell responses

Vaccine ◽  
2010 ◽  
Vol 28 (4) ◽  
pp. 922-933 ◽  
Author(s):  
Adan C. Jirmo ◽  
Richard C. Koya ◽  
Bala Sai Sundarasetty ◽  
Mudita Pincha ◽  
Guann-Yi Yu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Lentiviral Vectors ◽  
Cd8 T Cell ◽  
Structural Proteins ◽  
Cell Responses

O.107 Protective CD8+ T cell responses in hepatitis C virus infected/exposed individuals

2006 ◽  
Vol 36 ◽  
pp. S32
Author(s):  
M. Bharadwaj ◽  
T. Thammanichanond ◽  
C. Aitken ◽  
M. Hellard ◽  
S. Bowden ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses

scholarly journals Broadening CD4+ and CD8+ T Cell Responses against Hepatitis C Virus by Vaccination with NS3 Overlapping Peptide Panels in Cross-Priming Liposomes

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Jonathan Filskov ◽  
Marianne Mikkelsen ◽  
Paul R. Hansen ◽  
Jan P. Christensen ◽  
Allan R. Thomsen ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Recombinant Protein ◽  
T Cell Responses ◽  
T Cell Response ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Vaccine Approach

ABSTRACT Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad, vigorous CD4+ and CD8+ T cell responses are associated with control of acute hepatitis C. We employed a vaccine approach based on a mixture of peptides (pepmix) spanning the entire sequence of HCV nonstructural protein 3 (NS3) in cross-priming cationic liposomes (CAF09) to facilitate a versatile presentation of all possible T cell epitopes, regardless of the HLA background of the vaccine recipient. Here, we demonstrate that vaccination of mice with NS3 pepmix broadens the repertoire of epitope-specific T cells compared to the corresponding recombinant protein (rNS3). Moreover, vaccination with rNS3 induced only CD4+ T cells, whereas the NS3 pepmix induced a far more vigorous CD4+ T cell response and was as potent a CD8+ T cell inducer as an adenovirus-vectored vaccine expressing NS3. Importantly, the cellular responses are dominated by multifunctional T cells, such as gamma interferon-positive (IFN-γ+) tumor necrosis factor alpha-positive (TNF-α+) coproducers, and displayed cytotoxic capacity in mice. In conclusion, we present a novel vaccine approach against HCV, inducing a broadened T cell response targeting both immunodominant and potential subdominant epitopes, which may be key elements to counter T cell exhaustion and prevent chronicity. IMPORTANCE With at least 700,000 annual deaths, development of a vaccine against hepatitis C virus (HCV) has high priority, but the tremendous ability of the virus to dodge the human immune system poses great challenges. Furthermore, many chronic infections, including HCV infection, have a remarkable ability to drive initially strong CD4+ and CD8+ T cell responses against dominant epitopes toward an exhausted, dysfunctional state. Thus, new and innovative vaccine approaches to control HCV should be evaluated. Here, we report on a novel peptide-based nanoparticle vaccine strategy (NS3 pepmix) aimed at generating T cell immunity against potential subdominant T cell epitopes that are not efficiently targeted by vaccination with full-length recombinant protein (rNS3) or infection with HCV. As proof of concept, we found that NS3 pepmix excels in broadening the repertoire of epitope-specific, multifunctional, and cytotoxic CD4+ and CD8+ T cells compared to vaccination with rNS3, which generated only CD4+ T cell responses.

scholarly journals ERAP1 allotypes shape the epitope repertoire of virus-specific CD8+ T cell responses in acute hepatitis C virus infection

2019 ◽  
Vol 70 (6) ◽  
pp. 1072-1081 ◽  
Author(s):  
Janine Kemming ◽  
Emma Reeves ◽  
Katja Nitschke ◽  
Vanessa Widmeier ◽  
Florian Emmerich ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Virus Infection ◽  
Acute Hepatitis ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Acute Hepatitis C ◽  
Hepatitis C Virus Infection ◽  
Cell Responses

Longitudinal analysis of CD8 T-cell responses to HIV and hepatitis C virus in a cohort of co-infected haemophiliacs

AIDS ◽  
2005 ◽  
Vol 19 (11) ◽  
pp. 1135-1143 ◽  
Author(s):  
Gillian C Harcourt ◽  
Sharyne Donfield ◽  
Edward Gomperts ◽  
Eric S Daar ◽  
Philip JR Goulder ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Longitudinal Analysis ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses
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