Effects of Persistent Innate Immune Activation on Vaccine Efficacy

NCT ID: NCT02429583

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-08
• Study Completion Date: 2018-11-30

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.

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.

Conditions

Hepatitis C Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Recombivax in HCV infected individuals

Recombivax vaccine administered IM to HCV-infected individuals

Group Type: ACTIVE_COMPARATOR

Recombivax

Intervention Type: DRUG

Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment

Recombivax in healthy volunteers

Recombivax vaccine administered IM to healthy individuals

Group Type: ACTIVE_COMPARATOR

Recombivax

Intervention Type: DRUG

Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment

Interventions

Recombivax

Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment

Intervention Type: DRUG

Other Intervention Names

Hepatitis B vaccine

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 62 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Rockefeller University

OTHER

Sponsor Role: lead

Responsible Party

Charles Rice

Head of Laboratory of Virology and Infectious Disease

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles Rice, PhD

Role: PRINCIPAL_INVESTIGATOR

The Rockefeller University Center for Clinical and Translational

Locations

Rockefeller University Hospital

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U19AI111825

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CRI-0844

Identifier Type: -

Identifier Source: org_study_id