Hepatitis B
Conditions
Keywords
Hepatitis B, non responders, cellular immune response, cytokines, predictors, HBsAg
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.
Interventions
BIOLOGICALTwinrix
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.
Sponsors
Aarhus University Hospital
Monash Medical Centre
University of Aarhus
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Denmark
Outcome results
None listed