Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

This prospective, single-site, randomized, then open-label study is designed to develop a
detailed transcriptional and epigenetic profile of the immune response to pneumococcal
vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent
immune system of older adults. This knowledge may lead to development of more effective
vaccines through increased understanding of the effects of immunosenescence on mechanisms of
immune response to pneumococcal vaccination in the elderly.

Forty (40) healthy adults ages 65 and older that have never received pneumococcal
vaccination, will be randomized in a 1:1 ratio to receive Prevnar-13 (Pfizer), a conjugated
13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Following
randomized assignment of vaccine, the study will be open-label.The study sample will be drawn
from the population of healthy elderly in the catchment area of UConn Health in Farmington,
CT.

The first six (6) study visits are planned to occur over 67 days at Days -7, 0, 1, 10, 28 (±3
d) and 60 (± 5d). Participants will provide blood samples for transcriptional, epigenetic and
biological analyses pre- and post-vaccination.

One to two years after receiving the randomly-assigned vaccination, participants may opt to
receive administration of a second pneumococcal vaccine with the vaccine that they did not
receive by random assignment at Visit 2 (Day 0). This second vaccine will be provided at no
charge to the participant. Administration of this vaccine will occur at an optional Visit 7
for participants who choose to receive the second vaccine and will be scheduled at the
participant's convenience one-two years after receiving the first pneumococcal vaccine.

If the participant opts to receive the second vaccine within the study and attends optional
Visit 7, blood samples for genomic and biologic analysis will be collected at the visit.

Inclusion Criteria:

- Able and willing to provide written informed consent

- Male or Female, 65 years of age or older

- Willing to receive pneumococcal vaccination with Prevnar 13 (Wyeth/ Pfizer) or
Pneumovax 23 (Merck), as randomly assigned.

- Available to attend 6 study visits over 67 days (Visit 7 is optional at Day 365-720).

Exclusion Criteria:

- Previous pneumococcal vaccination with Prevnar 13 or Pneumovax 23.

- History of anaphylactic/anaphylactoid or severe allergic reaction to any component of
Pneumovax 23, Prevnar 13 or any diphtheria toxoid-containing vaccine.

- Established diagnosis of diabetes

- History of receiving Zostavax (shingles vaccine) within previous 4 weeks. (Study entry
may be delayed to satisfy a 28-day interval between vaccinations)

- Known history of any of the following co-morbid conditions:

- Malignancy (participants without a recurrence in the last 5 years will be
allowed)

- Congestive Heart Failure

- Cardiovascular Disease (unstable ≤ 6 months*)

- Kidney disease

- Renal failure

- Impaired hepatic function

- Autoimmune disease such as: Rheumatoid Arthritis, systemic lupus erythematosus
(SLE), Inflammatory Bowel Disease, etc.

- Use of medicines during past 6 months known to alter immune response such as
high-dose corticosteroids

- HIV, AIDS or other Immunodeficiency

- Recent (≤ 3 months) trauma or surgery

- Current substance and/or alcohol abuse * Unstable disease is defined as a change
in therapy or hospitalization for worsening disease.