Hepatitis B
Conditions
Keywords
Hepatitis B vaccine
Brief summary
Vaccines have been responsible for preventing millions of deaths and extending the average human lifespan. Effective vaccines stimulate the cells of the immune system to activate genes and associated functions that bring about protective immunity.This study aims to define cellular functions and genes important for the hepatitis B (HBV) vaccine immune response in healthy individuals. The investigators hypothesize that many genes associated with innate and adaptive immune functions are important for an effective HBV vaccine response.
Detailed description
Vaccines have been responsible for preventing millions of deaths and extending the average human lifespan. Effective vaccines stimulate the cells of the immune system to activate genes and associated functions that bring about protective immunity. Knowledge of those genes and cellular functions activated by effective vaccination can improve our understanding of how the immune system works and define the features necessary for a successful vaccine response. This study aims to define cellular functions important for the hepatitis B (HBV) vaccine immune response in healthy individuals. The investigators will identify those genes that are activated or suppressed in immune cells at various times after each dose of the HBV vaccine. The investigators will explore these vaccine-induced gene signatures to characterize the cellular functions associated with an effective immune response to HBV vaccination. The investigators hypothesize that many genes associated with innate and adaptive immune functions are important for an effective HBV vaccine response.
Interventions
BIOLOGICALHepatitis B Vaccine (Recombinant)
All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant).
Sponsors
Rockefeller University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteer without significant medical problems * Willing to receive three doses of an FDA-approved Hepatitis B vaccine
Exclusion criteria
* Male or female \< 18 and \> 60 years of age * Received any vaccine within a month prior to study vaccine * History of Hepatitis B infection * History of previous Hepatitis B vaccination(s) * History of Hepatitis C virus (HCV) infection or positive HCV antibody test * Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study * Positive serum antibody against Hep B surface antigen and/or core Hep B core antigen * human immunodeficiency virus (HIV) positive * In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol * Any clinically significant abnormality or medical history or physical examination including history of immunodeficiency or autoimmune disease * Is pregnant or lactating * Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications * Any clinically significant acute or chronic medical condition requiring care by a primary care provider (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation * Unable to continue participation for 30 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Day 1, Day 3, Week 1, and Week 2 | Number of differentially expressed genes at time point versus prevaccination baseline (p\<0.05). Following Principal Components Analysis, data from one participant series was identified as a technical outlier and excluded from downstream analyses. Differential gene expression analysis was conducted with the voom/limma tools in the R statistical framework. |
| Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Day 1, Day 3, Week 1, and Week 2 | Number of significantly differentially expressed genes at time point versus prevaccination baseline (FDR\<0.05). Following Principal Components Analysis, data from one participant series was identified as a technical outlier and excluded from downstream analyses. Differential gene expression analysis was conducted with the voom/limma tools in the R statistical framework. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hepatitis B Vaccination All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant).
Hepatitis B Vaccine (Recombinant): All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant). | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Prematurely Withdrawn | 1 |
Baseline characteristics
| Characteristic | Hepatitis B Vaccination |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 2 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction).
Number of differentially expressed genes at time point versus prevaccination baseline (p\<0.05). Following Principal Components Analysis, data from one participant series was identified as a technical outlier and excluded from downstream analyses. Differential gene expression analysis was conducted with the voom/limma tools in the R statistical framework.
Time frame: Day 1, Day 3, Week 1, and Week 2
Population: All participants received the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant). RNA-Seq (RNA sequencing) data from whole blood (PAXgene) for 9 participants were analyzed for differential gene expression at day 1, day 3, week 1, and week 2 after administration of the Hepatitis B Vaccine (Recombinant) (dose #1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Day 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Downregulated | 138 number of genes at p<0.05 |
| Day 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Upregulated | 316 number of genes at p<0.05 |
| Day 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Unchanged | 11139 number of genes at p<0.05 |
| Day 3 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Downregulated | 138 number of genes at p<0.05 |
| Day 3 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Upregulated | 137 number of genes at p<0.05 |
| Day 3 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Unchanged | 11318 number of genes at p<0.05 |
| Week 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Unchanged | 11189 number of genes at p<0.05 |
| Week 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Downregulated | 102 number of genes at p<0.05 |
| Week 1 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Upregulated | 302 number of genes at p<0.05 |
| Week 2 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Downregulated | 81 number of genes at p<0.05 |
| Week 2 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Upregulated | 151 number of genes at p<0.05 |
| Week 2 | Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction). | Unchanged | 11361 number of genes at p<0.05 |
Primary
Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing).
Number of significantly differentially expressed genes at time point versus prevaccination baseline (FDR\<0.05). Following Principal Components Analysis, data from one participant series was identified as a technical outlier and excluded from downstream analyses. Differential gene expression analysis was conducted with the voom/limma tools in the R statistical framework.
Time frame: Day 1, Day 3, Week 1, and Week 2
Population: All participants received the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant). RNA-Seq data from whole blood (PAXgene) for 9 participants were analyzed for differential gene expression at day 1, day 3, week 1, and week 2 after administration of the Hepatitis B Vaccine (Recombinant) (dose #1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Day 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Downregulated | 0 number of genes at FDR<0.05 |
| Day 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Upregulated | 0 number of genes at FDR<0.05 |
| Day 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Unchanged | 0 number of genes at FDR<0.05 |
| Day 3 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Downregulated | 0 number of genes at FDR<0.05 |
| Day 3 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Upregulated | 0 number of genes at FDR<0.05 |
| Day 3 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Unchanged | 0 number of genes at FDR<0.05 |
| Week 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Unchanged | 0 number of genes at FDR<0.05 |
| Week 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Downregulated | 0 number of genes at FDR<0.05 |
| Week 1 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Upregulated | 0 number of genes at FDR<0.05 |
| Week 2 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Downregulated | 0 number of genes at FDR<0.05 |
| Week 2 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Upregulated | 0 number of genes at FDR<0.05 |
| Week 2 | Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing). | Unchanged | 0 number of genes at FDR<0.05 |