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

Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01451801
• Other study ID #: SJF0001
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 10, 2011
• Last updated: October 25, 2012
• Start date: October 2011
• Est. completion date: July 2013

Study information

• Verified date: October 2012
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

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.

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Aarhus University Hospital	Aarhus N

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Monash Medical Centre

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization	Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-? producing CD4+ T cells	within 9. month from 1. vaccination	No
Secondary	Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml	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	No
Secondary	Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events	By evaluating adverse events described in Case Report Forms	Within 9 month from 1. vaccination	Yes
Secondary	Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization	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	No
Secondary	Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders	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	No
Secondary	Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay.	Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-? producing CD4+ T cells	18 month after 1. vaccination	No