Pilot Study: Gene Expression Profiling of Immune Response to HBV Vaccination in Healthy Volunteers

• Sponsor: Rockefeller University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02055365
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 10.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Biological: Hepatitis B Vaccine (Recombinant)	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Persistent Innate Immune Activation on Vaccine Efficacy Pilot Study: Gene Expression Profiling of Immune Response to HBV Vaccination in Healthy Volunteers
• Actual Study Start Date: Feb 18, 2014
• Actual Primary Completion Date: Jan 6, 2015
• Actual Study Completion Date: Jan 6, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hepatitis B vaccination All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant).	Biological: Hepatitis B Vaccine (Recombinant); All subjects will receive the standard 3-dose course of Recombivax HB (Merck) - Hepatitis B Vaccine (Recombinant).; Other Names: Recombivax HB - Merck & Co., Inc.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Rockefeller University	New York	New York	United States	10065

Sponsors and Collaborators

• Rockefeller University

Investigators

• Principal Investigator: Brad Rosenberg, MD, PhD, The Rockefeller University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brad Rosenberg, Whitehead Presidential Fellow, Rockefeller University
• ClinicalTrials.gov Identifier: NCT02055365
• Other Study ID Numbers: BRO-0828
• First Posted: Feb 5, 2014
• Last Update Posted: May 7, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Brad Rosenberg, Whitehead Presidential Fellow, Rockefeller University: Hepatitis B vaccine
• Additional relevant MeSH terms: Hepatitis B; Hepatitis

Study Results

Participant Flow

Arm/Group Title	Hepatitis B Vaccination
Arm/Group Description	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).
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Hepatitis B Vaccination
Arm/Group Description	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).
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	6 66.7%
Male	3 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 22.2%
Not Hispanic or Latino	5 55.6%
Unknown or Not Reported	2 22.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 11.1%
Asian	1 11.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 11.1%
White	3 33.3%
More than one race	0 0%
Unknown or Not Reported	3 33.3%

Outcome Measures

1. Primary Outcome

Title	Number of Differentially Expressed Genes at p < 0.05 (Without Multiple Testing Correction).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Day 1	Day 3	Week 1	Week 2
Arm/Group Description	Differentially expressed genes at Day 1 versus pre-vaccination baseline (p<0.05).	Differentially expressed genes at Day 3 versus pre-vaccination baseline (p<0.05).	Differentially expressed genes at Week 1 versus pre-vaccination baseline (p<0.05).	Differentially expressed genes at Week 2 versus pre-vaccination baseline (p<0.05).
Measure Participants	9	9	9	9
Downregulated	138	138	102	81
Unchanged	11139	11318	11189	11361
Upregulated	316	137	302	151

2. Primary Outcome

Title	Number of Significantly Differentially Expressed Genes at False Discovery Rate (FDR)< 0.05 (Upon Correction for Multiple Testing).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Day 1	Day 3	Week 1	Week 2
Arm/Group Description	Significantly Differentially expressed genes at Day 1 versus pre-vaccination baseline (FDR<0.05).	Significantly Differentially expressed genes at Day 3 versus pre-vaccination baseline (FDR<0.05).	Significantly Differentially expressed genes at Week 1 versus pre-vaccination baseline (FDR<0.05).	Significantly Differentially expressed genes at Week 2 versus pre-vaccination baseline (FDR<0.05).
Measure Participants	9	9	9	9
Downregulated	0	0	0	0
Unchanged	0	0	0	0
Upregulated	0	0	0	0

Adverse Events

Arm/Group Title	Hepatitis B Vaccination
Arm/Group Description	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).
All Cause Mortality
	Hepatitis B Vaccination
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Serious Adverse Events
	Hepatitis B Vaccination
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Hepatitis B Vaccination
	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)
Nervous system disorders
light headedness	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Scratchy Throat	1/9 (11.1%)
Skin and subcutaneous tissue disorders
mild ecchymosis	1/9 (11.1%)

Limitations/Caveats

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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.