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.
Brief Title
Effects of Persistent Innate Immune Activation on Vaccine Efficacy
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hepatitis C Infection
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
62 Years
Minimum Age
18 Years
NCT Id
NCT02429583
Org Class
Other
Org Full Name
Rockefeller University
Org Study Id
CRI-0844
Overall Status
Terminated
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Effects of Persistent Innate Immune Activation on Vaccine Efficacy
Primary Outcomes
Outcome 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
Luminex assay for multiplex cytokine/chemokine panel measured at 8 months RNA-Seq with analysis focus on curated ISG list measured at 8 months
Outcome Measure
HBV Vaccine Response Versus Non-response Status
Outcome Time Frame
8 months
Secondary Ids
Secondary Id
U19AI111825
Secondary Outcomes
Outcome Description
ELISPOT assays will measured at 8 months
Outcome Time Frame
8 months
Outcome Measure
Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time
Outcome Description
Flow cytometry assays measured at 8 months
Outcome Time Frame
8 months
Outcome Measure
Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells
Outcome Description
Isolated from patient PBMCs measured at 8 months
Outcome Time Frame
8 months
Outcome Measure
Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant
Outcome Description
Isolated from patient PBMCs measured at 8 months
Outcome Time Frame
8 months
Outcome Measure
Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
62
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Magdalena Slosar-Cheah
Investigator Email
mslosar@montefiore.org
Investigator Phone
Categories Mesh Debug
Hepatitis --- HEPATITIS C
Blood Disorders --- BLOOD-BORNE INFECTIONS
HIV/AIDS --- BLOOD-BORNE INFECTIONS
Infectious Disease --- BLOOD-BORNE INFECTIONS
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
Hepatitis --- HEPATITIS, VIRAL, HUMAN
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
Hepatitis --- HEPATITIS
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
MeSH Terms
HEPATITIS C
BLOOD-BORNE INFECTIONS
COMMUNICABLE DISEASES
INFECTIONS
HEPATITIS, VIRAL, HUMAN
VIRUS DISEASES
FLAVIVIRIDAE INFECTIONS
RNA VIRUS INFECTIONS
HEPATITIS
LIVER DISEASES
DIGESTIVE SYSTEM DISEASES
RECOMBIVAX HB
HEPATITIS B VACCINES
VIRAL HEPATITIS VACCINES
VIRAL VACCINES
VACCINES
BIOLOGICAL PRODUCTS
COMPLEX MIXTURES