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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hepatitis B vaccination | Experimental | All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hepatitis B Vaccine (Recombinant) | Biological | All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1, Day 3, Week 1, and Week 2 |
| 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. | Day 1, Day 3, Week 1, and Week 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brad Rosenberg, MD, PhD | The Rockefeller University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Rockefeller University | New York | New York | 10065 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Hepatitis B Vaccination | All subjects will receive the standard 3-dose course of Recombivax Hepatitis B (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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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). | Posted | Number | number of genes at p<0.05 | Day 1, Day 3, Week 1, and Week 2 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Scratchy Throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
Although RNA-Seq analysis was effective in measuring gene expression levels, additional study subjects (more samples) may have improved statistical power to detect subtle changes in gene expression over time post-vaccination.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brad Rosenberg, MD, PhD | Icahn School of Medicine at Mount Sinai | brad.rosenberg@mssm.edu |
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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 |
|---|---|
| D017325 | Hepatitis B Vaccines |
| ID | Term |
|---|---|
| D014761 | Viral Hepatitis Vaccines |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
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|
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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Differentially expressed genes at Day 1 versus pre-vaccination baseline (p<0.05).
| OG001 | Day 3 | Differentially expressed genes at Day 3 versus pre-vaccination baseline (p<0.05). |
| OG002 | Week 1 | Differentially expressed genes at Week 1 versus pre-vaccination baseline (p<0.05). |
| OG003 | Week 2 | Differentially expressed genes at Week 2 versus pre-vaccination baseline (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. | 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). | Posted | Number | number of genes at FDR<0.05 | Day 1, Day 3, Week 1, and Week 2 |
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| 0 |
| 9 |
| 0 |
| 9 |
| 2 |
| 9 |
| mild ecchymosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| light headedness | Nervous system disorders | Non-systematic Assessment |
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| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D045424 |
| Complex Mixtures |
| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Unchanged |
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| Upregulated |
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