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| Name | Class |
|---|---|
| Aarhus University Hospital | OTHER |
| Monash Medical Centre | OTHER |
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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:
To estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization
Secondary aims:
To establish the prevalence of serological non-responders after a standard course of HBV vaccination.
To assess the safety of the vaccine.
Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
To compare the immunological profile before and after a standard HBV vaccination regimen on non-responders and responders
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HBsAg | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Twinrix | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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-γ producing CD4+ T cells | within 9. month from 1. vaccination |
| 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 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lars Østergaard, Head | Department of Infectious Diseases, Aarhus University Hospital | Study Chair |
| Søren Jensen-Fangel, MD | Department of Infectious Diseases, Aarhus University Hospital | Study Director |
| Martin Tolstrup, MSc | Department of Infectious Diseases, Aarhus University Hospital | Study Director |
| Maria B Pedersen, Bach.Med | Department of Infectious Diseases, Aarhus University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Infectious Diseases, Aarhus University Hospital | Aarhus N | 8200 | Denmark |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| ID | Term |
|---|---|
| C433226 | twinrix |
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|
| 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 |
| 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 |
| 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 |
| 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-γ producing CD4+ T cells | 18 month after 1. vaccination |
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |