Study of the Cellular Response Induced After Vaccination Against the Hepatitis B Virus

Not yet recruiting

• Conditions: Hepatitis B Vaccination; Immune Response; T Cells

• Registration Number: NCT06876467
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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 The first generation of plasma-based vaccines, introduced in the 1980s, has now been superseded by protein vaccines, which are the only ones authorized in France.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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-10
• Study First Submitted QC: 2025-03-10
• Last Update Submitted: 2025-03-10
• Study First Posted: 2025-03-14
• Last Update Posted: 2025-03-14
• Study Start: 2025-04-01
• Primary Completion: 2028-07-01
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 115

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of individuals with a cellular response	At inclusion	Proportion of individuals with a cellular response directed against HBsAg following HBV vaccination At inclusion, 5 to 10 weeks after HBV vaccination

Secondary Outcome Measures

Name	Time	Method
Frequency of pehotypes of T lymphocytes post-HBV vaccination	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
Anti-HBsAg antibody levels	At inclusion	Before and after vaccination 4 weeks prior to vaccination and 5 to 10 weeks after vaccination
Percentage of LT CD4 circulating cells	At inclusion	5 to 10 weeks after vaccination
Percentage of LT CD8 circulating cells	At inclusion	5 to 10 weeks after vaccination