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

October 25, 2012 updated by: University of Aarhus

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • Department of Infectious Diseases, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: HBsAg
Biological: Twinrix

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.

Twinrix ® Adult suspension for injection. 1 ml contains 720 ELISA units of hepatitis A virus antigen adsorbed to aluminum hydroxide and 20 micrograms hepatitis B surface antigen (HBsAg) adsorbed to aluminum phosphate in sterile water. Excipient: sodium chloride. Contains traces of neomycin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization
Time Frame: 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
within 9. month from 1. vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml
Time Frame: 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
Within 9 month from 1. vaccination
Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events
Time Frame: Within 9 month from 1. vaccination
By evaluating adverse events described in Case Report Forms
Within 9 month from 1. vaccination
Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
Time Frame: 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 .
within 9 month from 1. vaccination
Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders
Time Frame: 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 .
Within 9. month from 1. vaccination
Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay.
Time Frame: 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
18 month after 1. vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital
Monash Medical Centre

Investigators

  • Study Chair: Lars Østergaard, Head, Department of Infectious Diseases, Aarhus University Hospital
  • Study Director: Søren Jensen-Fangel, MD, Department of Infectious Diseases, Aarhus University Hospital
  • Study Director: Martin Tolstrup, MSc, Department of Infectious Diseases, Aarhus University Hospital
  • Principal Investigator: Maria B Pedersen, Bach.Med, Department of Infectious Diseases, Aarhus University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Anticipated)

July 1, 2013

Study Completion (Anticipated)

July 1, 2013

Study Registration Dates

First Submitted

October 10, 2011

First Submitted That Met QC Criteria

October 13, 2011

First Posted (Estimate)

October 14, 2011

Study Record Updates

Last Update Posted (Estimate)

October 26, 2012

Last Update Submitted That Met QC Criteria

October 25, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SJF0001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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