Study of the Cellular Response Induced After Vaccination Against the Hepatitis B Virus (HBVax)
Etude de la réponse Cellulaire Induite Post-vaccination Contre le Virus de l'hépatite B
296 million people worldwide are infected with the hepatitis B virus (HBV), despite the existence of an effective prophylactic vaccine. Current treatments (nucleoside analogues and pegylated interferon-α) do not prevent chronic hepatitis B (CHB) patients from developing liver fibrosis or hepatocellular carcinoma.
Vaccination is the best way to prevent HBV infection. The first generation of plasma-based vaccines, introduced in the 1980s, has now been superseded by protein vaccines, which are the only ones authorized in France. They are safe and effective. After an initial series of three out of four doses, protective levels of antibodies to the HBV surface antigen (anti-HBsAg; ≥10 IU/mL) are achieved in over 95% of infants, children and young adults.
HBV antigen (Ag)-specific CD4+ and CD8+ T lymphocytes play a major role in the control of HBV infection, contributing to viral clearance and the pathophysiology of acute hepatitis B. However, during HBC, these HBV-specific T cells develop a dysfunctional phenotype and become 'exhausted'. T lymphocytes directed against surface protein antigens (HBsAg) are the most affected by depletion mechanisms - these disappear completely in chronically infected patients, suggesting an important role for these T lymphocytes in infection control. Interestingly, recent studies of rare patients undergoing functional recovery from chronic infection following antiviral treatment have shown a re-emergence of T lymphocytes directed against HBsAg, confirming the importance of these cells in controlling viral replication. Although the protection induced by hepatitis B vaccination has mainly been attributed to the humoral response, a few studies have documented the presence of HBsAg-specific T lymphocytes. These could contribute to the maintenance of a long-term post-vaccination humoral response. The aim of this study is therefore to determine the frequency of healthy individuals receiving HBV vaccination who have a detectable HBsAg-specific T-cell response post-vaccination. We will also study the potential correlation between the frequency of HBsAg-specific T lymphocytes and the level of serum anti-HBsAg antibodies, and we will finely characterize the functional phenotype of these cells using cutting-edge methods and technologies (spectral cytometry, sequencing of mRNA and TCRs). These data will contribute to a better understanding of the biological mechanisms associated with HBV vaccine-induced protection.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Jérôme Lambert, MD PhD
- Phone Number: +33 142499742
- Email: jerome.lambert@u-paris.fr
Study Contact Backup
- Name: Jérôme Le Goff, MD PhD
- Phone Number: +33 1 42 49 94 93
- Email: jerome.le-goff@aphp.fr
Study Locations
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-
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Paris, France
- Recruiting
- Hôpital Saint Louis AP-HP
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Contact:
- Véronique Mahé, +33
- Phone Number: +33 +331 42 49 49 49
- Email: veronique.mahe@aphp.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adults ≥18 years
- Pre-vaccination HBV serology carried out within 4 weeks prior to vaccination
- Collection of no objection
Exclusion Criteria:
- Opposition of the person or inability to give opposition
- Pregnant or breast-feeding women
- Chronic illnesses affecting the individual's immune system (asplenia; hyposplenia; haematological cancer; auto-immune disease requiring immunosuppressive treatment, HIV infection).
- Non-affiliation with a social security scheme, Universal Medical Coverage or any equivalent scheme
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Healthy individuals receiving HBV vaccination
|
detection of HBsAg-specific T lymphocytes by spectral cytometry
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Proportion of individuals with a cellular response
Time Frame: At inclusion
|
Proportion of individuals with a cellular response directed against HBsAg following HBV vaccination At inclusion, 5 to 10 weeks after HBV vaccination
|
At inclusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Frequency of pehotypes of T lymphocytes post-HBV vaccination
Time Frame: At inclusion
|
Phenotypic and functional characterization of HBsAg-specific CD4+ and CD8+ T lymphocytes post-HBV vaccination Quantitative results obtained by spectral cytometry and RNA sequencing to characterise HBsAg-specific LTs 5 to 10 weeks after HBV vaccination
|
At inclusion
|
|
Anti-HBsAg antibody levels
Time Frame: At inclusion
|
Before and after vaccination 4 weeks prior to vaccination and 5 to 10 weeks after vaccination
|
At inclusion
|
|
Percentage of LT CD4 circulating cells
Time Frame: At inclusion
|
5 to 10 weeks after vaccination
|
At inclusion
|
|
Percentage of LT CD8 circulating cells
Time Frame: At inclusion
|
5 to 10 weeks after vaccination
|
At inclusion
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- APH241703
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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