Effects of Persistent Innate Immune Activation on Vaccine Efficacy

Sponsor
Rockefeller University (Other)
Overall Status
Terminated
CT.gov ID
NCT02429583
Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
24
1
2
41.8
0.6

Study Details

Study Description

Brief Summary

This study will investigate the effects of chronic HCV infection and corresponding innate immune activation on the immune response to HBV vaccination. We will recruit chronic HCV patients and healthy control patients for HBV vaccination. We will use RNA Sequencing (RNA-Seq), a relatively new technology for simultaneously measuring the expression of all genes, to determine patients' innate immune status, and learn how this innate immune signature is related to HBV vaccine response. We will then explore the mechanisms by which chronic HCV infection affects different immune cells and functions that are known to be important for an effective HBV vaccine response. These studies will enhance our understanding of the immune effects of chronic viral infection, establish factors that determine effective vaccine responses, and help guide vaccination strategies for HCV patients and other individuals with chronic inflammatory disease.

Condition or Disease Intervention/Treatment Phase
Phase 4

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. If we can better understand the factors that influence vaccine success versus failure, we may be able to improve current vaccines and/or develop new vaccines against prevalent infectious diseases.

Certain groups of people do not respond well to particular vaccines. For example, vaccines can be less effective in immunocompromised patients, elderly individuals, and people with chronic inflammatory diseases. Often it is these groups of people that have the greatest need for protection against infectious disease.

People chronically infected with hepatitis C virus (HCV) are at increased risk of serious liver disease. As a result, they should receive the hepatitis B virus (HBV) vaccine, which can protect them from infection by HBV, another virus that targets the liver. However, people chronically infected with HCV do not respond to the HBV vaccine as effectively as healthy people without HCV. Chronic HCV infection is not thought to cause general problems with the immune system, and the reasons for this poor vaccine response are poorly understood. Previous work has shown that chronic HCV infection leads to production of chemical ("innate immune") signals that can affect function of the immune system, but it is currently unknown how this might impact vaccination.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Effects of Persistent Innate Immune Activation on Vaccine Efficacy
Actual Study Start Date :
May 8, 2015
Actual Primary Completion Date :
Nov 1, 2018
Actual Study Completion Date :
Nov 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Recombivax in HCV infected individuals

Recombivax vaccine administered IM to HCV-infected individuals

Drug: Recombivax
Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
Other Names:
  • Hepatitis B vaccine
  • Active Comparator: Recombivax in healthy volunteers

    Recombivax vaccine administered IM to healthy individuals

    Drug: Recombivax
    Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Other Names:
  • Hepatitis B vaccine
  • Outcome Measures

    Primary Outcome Measures

    1. HBV Vaccine Response Versus Non-response Status [8 months]

      Titers of anti-hepatitis B surface antigen antibody measured at 8 months Luminex assay for multiplex cytokine/chemokine panel measured at 8 months RNA-Seq with analysis focus on curated ISG list measured at 8 months

    Secondary Outcome Measures

    1. Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time [8 months]

      ELISPOT assays will measured at 8 months

    2. Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells [8 months]

      Flow cytometry assays measured at 8 months

    3. Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant [8 months]

      Isolated from patient PBMCs measured at 8 months

    4. Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq [8 months]

      Isolated from patient PBMCs measured at 8 months

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 62 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Willing to receive three doses of an FDA-approved Hepatitis B vaccine

    • Volunteer chronically infected with HCV (as demonstrated by serology and/or viral load laboratory studies)

    • Healthy volunteer without significant medical problems

    Exclusion Criteria:
    • Received any vaccine within a month prior to study vaccine

    • Positive serum antibody against Hep B surface antigen and/or core Hep B core antigen

    • HIV positive

    • For HCV-negative, healthy volunteers: History of 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

    • 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 (in addition to HCV infection, for HCV group)

    • 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 156 weeks

    • History of previous Hepatitis B vaccination(s)

    • Male or female < 18 and > 62 years of age

    • Is pregnant or lactating

    • History of Hepatitis B infection

    • Clinical, laboratory, or biopsy evidence of cirrhosis

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Rockefeller University
    • National Institute of Allergy and Infectious Diseases (NIAID)

    Investigators

    • Principal Investigator: Charles Rice, PhD, The Rockefeller University Center for Clinical and Translational

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Charles Rice, Head of Laboratory of Virology and Infectious Disease, Rockefeller University
    ClinicalTrials.gov Identifier:
    NCT02429583
    Other Study ID Numbers:
    • CRI-0844
    • U19AI111825
    First Posted:
    Apr 29, 2015
    Last Update Posted:
    Mar 4, 2020
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Period Title: Overall Study
    STARTED 1 23
    COMPLETED 1 3
    NOT COMPLETED 0 20

    Baseline Characteristics

    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers Total
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Total of all reporting groups
    Overall Participants 1 3 4
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    100%
    3
    100%
    4
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    60
    44
    48
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    1
    100%
    3
    100%
    4
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    1
    100%
    2
    66.7%
    3
    75%
    Unknown or Not Reported
    0
    0%
    1
    33.3%
    1
    25%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    100%
    0
    0%
    1
    25%
    White
    0
    0%
    2
    66.7%
    2
    50%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    33.3%
    1
    25%
    Region of Enrollment (participants) [Number]
    United States
    1
    100%
    3
    100%
    4
    100%

    Outcome Measures

    1. Primary Outcome
    Title HBV Vaccine Response Versus Non-response Status
    Description Titers of anti-hepatitis B surface antigen antibody measured at 8 months Luminex assay for multiplex cytokine/chemokine panel measured at 8 months RNA-Seq with analysis focus on curated ISG list measured at 8 months
    Time Frame 8 months

    Outcome Measure Data

    Analysis Population Description
    The data was not collected and the analysis was not completed for this study due to insufficient enrollment.
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Measure Participants 0 0
    2. Secondary Outcome
    Title Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time
    Description ELISPOT assays will measured at 8 months
    Time Frame 8 months

    Outcome Measure Data

    Analysis Population Description
    The data was not collected and the analysis was not completed for this study due to insufficient enrollment.
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Measure Participants 0 0
    3. Secondary Outcome
    Title Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells
    Description Flow cytometry assays measured at 8 months
    Time Frame 8 months

    Outcome Measure Data

    Analysis Population Description
    The data was not collected and the analysis was not completed for this study due to insufficient enrollment.
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Measure Participants 0 0
    4. Secondary Outcome
    Title Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant
    Description Isolated from patient PBMCs measured at 8 months
    Time Frame 8 months

    Outcome Measure Data

    Analysis Population Description
    The data was not collected and the analysis was not completed for this study due to insufficient enrollment.
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Measure Participants 0 0
    5. Secondary Outcome
    Title Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq
    Description Isolated from patient PBMCs measured at 8 months
    Time Frame 8 months

    Outcome Measure Data

    Analysis Population Description
    The data was not collected and the analysis was not completed for this study due to insufficient enrollment.
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    Measure Participants 0 0

    Adverse Events

    Time Frame Up to 30 weeks
    Adverse Event Reporting Description Adverse event information was collected from both arms of the study (3 healthy volunteers and 1 HCV infected individual)
    Arm/Group Title Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Arm/Group Description Recombivax vaccine administered IM to HCV-infected individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment Recombivax vaccine administered IM to healthy individuals Recombivax: Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
    All Cause Mortality
    Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/3 (0%)
    Serious Adverse Events
    Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Recombivax in HCV Infected Individuals Recombivax in Healthy Volunteers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 2/3 (66.7%)
    General disorders
    Cold Like Symptoms 0/1 (0%) 1/3 (33.3%) 1
    Patient Stubbed Toe 0/1 (0%) 1/3 (33.3%) 1
    Surgical and medical procedures
    Pain at Injection Site 0/1 (0%) 1/3 (33.3%) 1

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Aileen O'Connell, Laboratory Manager
    Organization The Rockefeller University
    Phone 212-327-7047
    Email aoconnell@rockefeller.edu
    Responsible Party:
    Charles Rice, Head of Laboratory of Virology and Infectious Disease, Rockefeller University
    ClinicalTrials.gov Identifier:
    NCT02429583
    Other Study ID Numbers:
    • CRI-0844
    • U19AI111825
    First Posted:
    Apr 29, 2015
    Last Update Posted:
    Mar 4, 2020
    Last Verified:
    Feb 1, 2020