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Effects of Persistent Innate Immune Activation on Vaccine Efficacy

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ClinicalTrials.gov Identifier: NCT02429583
Recruitment Status : Terminated (Unable to enroll sufficient subjects)
First Posted : April 29, 2015
Results First Posted : March 4, 2020
Last Update Posted : March 4, 2020
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Charles Rice, Rockefeller University

Study Description
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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
Hepatitis C Infection Drug: Recombivax 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
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Study Type : Interventional  (Clinical Trial)
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 : November 2018
Actual Study Completion Date : November 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Hepatitis B vaccine


Outcome Measures
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Primary Outcome Measures :
  1. HBV Vaccine Response Versus Non-response Status [ Time Frame: 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 [ Time Frame: 8 months ]
    ELISPOT assays will measured at 8 months

  2. Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells [ Time Frame: 8 months ]
    Flow cytometry assays measured at 8 months

  3. Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant [ Time Frame: 8 months ]
    Isolated from patient PBMCs measured at 8 months

  4. Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq [ Time Frame: 8 months ]
    Isolated from patient PBMCs measured at 8 months


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 62 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02429583


Locations
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United States, New York
Rockefeller University Hospital
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Charles Rice, PhD The Rockefeller University Center for Clinical and Translational
  Study Documents (Full-Text)

Documents provided by Charles Rice, Rockefeller University:
Study Protocol and Statistical Analysis Plan  [PDF] December 8, 2018

More Information
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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 ( U.S. NIH Grant/Contract )
First Posted: April 29, 2015    Key Record Dates
Results First Posted: March 4, 2020
Last Update Posted: March 4, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Blood-Borne Infections
Communicable Diseases
Infections
 Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs