Immunity to Hepatitis B Vaccine

Study Overview
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Brief Summary
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Infection and cancer is a major cause of death and morbidity, and may be preventable through vaccination. It is not fully understood at the molecular level why some people respond better than others to vaccines until now the technology to assess this has not been available. This has impaired vaccine development. The overall goal of the Human Vaccines Project is to understand the 'rules' of how vaccines work. In this demonstration project the investigators will vaccinate healthy adults with hepatitis B vaccine to start to understand better how it works, ultimately helping with rational vaccine design in the future.

Official Title
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Identification of Age-dependent Mechanism of Vaccine-induced Immunity to a Single Dose of Hepatitis B Vaccine Using a Systems Biology Approach - a Demonstration Project

Conditions
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Hepatitis B, Immunization; Infection

Intervention / Treatment
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* Drug: Hepatitis B vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult, corresponding to one of the study age groups. No history of hepatitis B disease. No prior receipt of any hepatitis B-containing vaccine. Undetectable level of anti-HBs and anti-HBc antibody and HBs antigen at study enrolment (indicating no evidence of prior hepatitis B vaccination or infection). Generally good health (stable chronic conditions acceptable), living independently or with minimal assistance (Clinical Frailty score 1-5) and able to attend clinic appointments. Willing and able to comply with the requirements of the protocol. Has given informed consent for participation in the study. Exclusion Criteria: The participant may not enter the study if ANY of the following apply: Individual who is on the delegation log for this study History of being a household contact of a known hepatitis B-infected individual. Planned administration of any vaccine not specified in the study protocol from 1 month pre- to the 1 month post-1st dose of vaccine. Planned receipt of any investigational drug for the duration of the study. Confirmed or suspected immunodeficiency. A family history of congenital or hereditary immunodeficiency. Receipt of more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid) in the 3 months prior to dose 1 of vaccine. Nasal, topical or inhaled steroids are allowed. Currently taking any anti-platelet or anti-coagulant medications (does not include daily low-dose aspirin). Bleeding disorder or thrombocytopenia, that contraindicates IM injection, blood collection and/or lymph node fine needle aspiration. Administration of immunoglobulins within the prior 12 months and/or any other blood products within the prior 3 months or planned during the study period. Current pregnancy or planning to become pregnant in the 6 months post-dose 1 vaccination. History of allergy to any component of the vaccine. Unstable medical condition, as indicated by a requirement for hospitalization or a substantial medication change to stabilize said condition within previous 3 months. History of any neurologic disorders or seizures, including a history of Guillain-Barre syndrome. Clinical Frailty score of 6-7 (moderately frail or severely frail). Scheduled elective surgery or other procedures requiring general anaesthesia from 1 month pre- to the 1 month post-1st dose of vaccine. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. Temporary exclusion if acute symptomatic illness in the 7 days prior to planned first vaccine dose - vaccination will be delayed, but participant can remain in the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>Older adults, aged 61-80 years | Drug: Hepatitis B vaccine<br>* 1.0 ml (20 micrograms) suspension of hepatitis B surface antigen for intramuscular injection<br>* Other names: ENGERIX®-B;|
| Other: Group 2<br>Younger adults, aged 40-60 years | Drug: Hepatitis B vaccine<br>* 1.0 ml (20 micrograms) suspension of hepatitis B surface antigen for intramuscular injection<br>* Other names: ENGERIX®-B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody response to the first dose of hepatitis B vaccine | Anti-HBs antibody level | 28 days post-vaccination following the first dose of vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to cellular immune response | Immunophenotyping by flow cytometric analysis of immune cell populations, including antigen-specific T-cell and B-cell responses, and response of immune cells to various stimuli in vitro | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination | 
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to transcriptomic response | Gene expression by RNA sequencing of whole blood and single immune cells | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination | 
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to proteomic response | Proteomic analysis of plasma and white blood cells | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination | 
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to metabalomic response | Metabolomic analysis of plasma | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination | 
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to epigenetic response | Epigenetic changes in genome | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination | 
| Kinetics of the immune response to the first dose of hepatitis B vaccine with respect to lymph node response | Immune responses in local lymph node, and comparison with peripheral blood responses | Pre-vaccine and 14 days following first dose only | 
| Identify the DNA sequence of B- and T- cell receptors following vaccination | DNA sequencing of T- and B- cells | Baseline (pre-vaccine) and on days 1, 3, 7 and 14 post-vaccination |