Effects of Persistent Innate Immune Activation on Vaccine Efficacy

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.

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