Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders

Phase 4

• Conditions: Hepatitis B
• Interventions: Biological: Twinrix

• Registration Number: NCT01451801
• Lead Sponsor: University of Aarhus

Brief Summary

Previous studies have shown that 5-10% of Hepatitis B Virus vaccine recipients produce none or to few antibodies after a standard immunization with 3 vaccines. These individuals are defined as non-responders. The investigators wish to investigate if mounting another kind of immune response, called the cellular immune (CMI) response, protects these non-responders.

Aim/Hypothesis

Primary aims:

1. To estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization

Secondary aims:

2. To establish the prevalence of serological non-responders after a standard course of HBV vaccination.

3. To assess the safety of the vaccine.

4. Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization

5. To compare the immunological profile before and after a standard HBV vaccination regimen on non-responders and responders

6. Establish a rapid test for measuring CMI after being HBV vaccinated.

A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months. Blood is drawn at 0 and 8 months from all participants. The blood will be analysed to see if there is antibodies or/and if there is mounted a cellular immune response by measuring on parameters called cytokines.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-10-10
• Study First Submitted QC: 2011-10-13
• Study First Posted: 2011-10-14
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-25
• Last Update Posted: 2012-10-26
• Primary Completion: 2013-07
• Study Completion: 2013-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Signed participant information and consent
• Age over 18 years
• Women of childbearing potential must use effective contraceptives

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Exclusion Criteria

• previous HBV infection
• previous HBV immunization
• pregnancy (or planned pregnancy within 6 months)
• allergy to contents in the vaccine (formaldehyde).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HBsAg	Twinrix	-

Primary Outcome Measures

Name	Time	Method
Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization	within 9. month from 1. vaccination	Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells

Secondary Outcome Measures

Name	Time	Method
Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml	Within 9 month from 1. vaccination	Antibodies to Hepatitis B surface antigen are detected by use of a comercially available kit at the department of Clinical Immunology, Aarhus University Hospital, Skejby
Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events	Within 9 month from 1. vaccination	By evaluating adverse events described in Case Report Forms
Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization	within 9 month from 1. vaccination	Questionnaire and \*Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells \*HBsAg-specific T cell proliferation is quantified\*The difference in phenotypic T cell profiles is getting compared at baseline\*HBsAg-specific B cells measured by flow cytometry with staining for surface markers\*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines\* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .
Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders	Within 9. month from 1. vaccination	Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells \*HBsAg-specific T cell proliferation is quantified\*The difference in phenotypic T cell profiles is getting compared at baseline\*HBsAg-specific B cells measured by flow cytometry with staining for surface markers\*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines\* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .
Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay.	18 month after 1. vaccination	Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells

Trial Locations

Locations (1)

Department of Infectious Diseases, Aarhus University Hospital; 🇩🇰 Aarhus N, Denmark