Effects of Persistent Innate Immune Activation on Vaccine Efficacy

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Recombivax

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Rockefeller University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 62 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBV Vaccine Response Versus Non-response Status	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	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time	ELISPOT assays will measured at 8 months	8 months
Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells	Flow cytometry assays measured at 8 months	8 months
Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant	Isolated from patient PBMCs measured at 8 months	8 months
Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq	Isolated from patient PBMCs measured at 8 months	8 months

Collaborators and Investigators

• Sponsor: Rockefeller University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Charles Rice, PhD, The Rockefeller University Center for Clinical and Translational

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2015
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: April 24, 2015
• First Submitted That Met QC Criteria: April 24, 2015
• First Posted (Estimate): April 29, 2015

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: February 20, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CRI-0844; U19AI111825 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED