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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Aarhus University Hospital
Monash Medical Centre
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01451801
First received: October 10, 2011
Last updated: October 25, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Hepatitis B
 Biological: Twinrix
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization [ Time Frame: within 9. month from 1. vaccination ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 9 month from 1. vaccination ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: within 9 month from 1. vaccination ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 9. month from 1. vaccination ] [ Designated as safety issue: No ]
    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. [ Time Frame: 18 month after 1. vaccination ] [ Designated as safety issue: No ]
    Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells


Estimated Enrollment: 400
Study Start Date: October 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01451801

Locations
Denmark
Department of Infectious Diseases, Aarhus University Hospital
Aarhus N, Denmark, 8200
Sponsors and Collaborators
University of Aarhus
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
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01451801     History of Changes
Other Study ID Numbers: SJF0001
Study First Received: October 10, 2011
Last Updated: October 25, 2012
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by University of Aarhus:
Hepatitis B
non responders
cellular immune response
 cytokines
predictors
HBsAg

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
 Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on May 19, 2013