Systems Biology of Zoster Vaccine (ZOSTAVAX®) in Young and Elderly

RATIONALE: Zoster vaccine is known to induce diminished antigen-specific T cell responses and
lower protection in the elderly. Here we hypothesize that this is due to intrinsic defects in
innate responses to the live attenuated virus, which translates into sub-optimal functional
adaptive immune responses. Therefore, early innate signatures of vaccination should correlate
with, and predict the immunogenicity of Zoster vaccine in the young and elderly.

STUDY DESIGN: Double center, open label study in which adult healthy volunteers will be
vaccinated with Zoster vaccine. Blood samples will be collected on day D-30 (pre-
vaccination) D0 (at vaccination) and D1, D3, D7, D14, D30, D90 and D180 (post vaccination) to
study innate and adaptive immunity responses. Even though Zoster vaccine is considered safe,
volunteers are asked to report and record any local or systemic AEs for 7 days
post-vaccination. Also AEs will be reported for 30 days post-vaccination any SAE for 180 days
post vaccination. AEs developing the day of the blood draw will also be reported

Inclusion Criteria:

- Able to understand and give informed consent.

- Immunocompetent subjects aged 25-40 years, or community dwelling subjects between the
ages of 60-79.

Exclusion Criteria:

- Young adults aged 25-40 years who are Varicella-Zoster virus seronegative or equivocal
results (mean value OD for Varicella-Zoster virus IgG lower than 1.1 by commercial
enzyme-linked immunosorbent assay (ELISA) (Hope Clinic: IgG VZV ELISAII-Wampole
Laboratories®, NJ, USA- Vaccine Research Trials Center:: Liaison VZV IgG Assay,
DiaSorin, Italy)

- Receipt of immune products:

- Receipt of blood products within 6 months prior to vaccination with Zoster
vaccine or expected receipt through 6 months after vaccination with Zoster
vaccine*

- Receipt of any vaccine within 4 weeks prior to vaccination with Zoster vaccine or
expected receipt within 4 weeks after vaccination with Zoster vaccine*

- Receipt of Zoster vaccine or varicella vaccines at any time prior to study entry.

- Subject taking any non-topical antiviral therapy with activity against herpes viruses,
including but not limited to acyclovir, famciclovir, valacyclovir, and ganciclovir 3
days prior to vaccination or 14 days after*.

- Prior history of shingles.

- Presence of certain co morbidities or immunosuppressive states such as:

- Chronic medical problems including (but not limited to) insulin-dependent
diabetes, severe heart, lung, liver, or kidney diseases; auto immune diseases;
severe gastrointestinal diseases; and uncontrolled hypertension.

- Alcohol or drug abuse and psychiatric conditions that in the opinion of the
investigator would preclude compliance with the trial or interpretation of safety
or endpoint data.

- Impaired immune function or chronic infections including (but not limited to)
HIV, hepatitis B or C, tuberculosis, organ transplant, cancer, current and or
expected receipt of chemotherapy, radiation therapy, steroids [i.e., > 20 mg of
prednisone given daily or on alternative days for 2 weeks or more in the past 90
days*); (nasal and topical steroids are allowed)],antitumor necrosis factor
agents, or any other immunosuppressive therapy, anatomic or functional asplenia,
congenital immunodeficiency.

- Pregnant or breast-feeding women, or women expecting to conceive 30 days before
and 90 days after vaccination**.

- Conditions that could affect the safety of the volunteers such as:

- Severe reactions to prior vaccinations.

- History of anaphylactic/anaphylactoid reaction to gelatin, neomycin or any other
component of the vaccine. Neomycin allergy manifested as contact dermatitis is
not a contraindication to receiving this vaccine.

- History of bleeding disorders

- Any acute illness, including any fever (> 100.4 F [> 38.0C], regardless of the route)
within 3 days prior to study entry *.

- Social, occupational, or any other condition that in the opinion of the investigator
might interfere with compliance with the study and vaccine evaluation.

Note:

*An individual who initially is excluded from study participation based on one or more of
the time-limited exclusion criteria (e.g., acute illness, receipt or expected receipt of
live or inactivated vaccines ) may be considered for enrollment once the condition has
resolved as long as the subject continues to meet all other entry criteria.

Subjects receiving > 20 mg/day of prednisone or its equivalent daily or on alternate days
for more than 2 weeks may enter the study after therapy has been discontinued for more than
3 months.

**Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral
oophorectomy or hysterectomy or who are not postmenopausal for ≥1 year) must agree to
practice adequate contraception that may include, but is not limited to, relationship with
vasectomized partner, barrier methods such as condoms, diaphragms, spermicides,
intrauterine devices, and licensed hormonal methods for 30 days before and 90 days after
zoster vaccination.