Pneumococcal Adult-dose Ranging Immunization Study

The purpose of this prospective randomized study is to assess the safety, post-vaccination
antibody response, and memory response to a subsequent polysaccharide challenge of varying
doses of PCV7 compared with the standard dose of PPV23 in immunocompetent adults 70-79 years
of age who were previously vaccinated with PPV23 at age 65 years or above and at least 5
years previously. The study will be conducted among a total of 220 persons recruited from GHC
and the Seattle VAMC. Participants will be randomized into one of 5 study groups with 44
participants per group. The antigen content of PCV7 will be varied by administration of
different volumes of the licensed pediatric formulation of that vaccine. Four groups will
receive one of four volumes (0.1 mL, 0.5 mL, 1.0 mL, 2.0 mL) of the licensed pediatric
formulation of PCV7 followed 12 months later by administration of a challenge 0.1 mL dose of
PPV23 to assess the induction of immunologic memory. The comparison group will receive the
standard 0.5 mL dose of PPV23 following 12 months later by administration of a 0.1 mL dose of
PPV23.

Inclusion Criteria:

- Age 70 through 79 years (up to the day prior to the 80th birthday)

- Previously received exactly one dose of PPV23, and that dose was received on or after
their 65th birthday and at least 5 years before the date of study enrollment

- Expected to reside in the area for at least 13 months

- Able to understand and give informed consent

- Able to perform study procedures

- Able to be contacted by telephone for follow-up on adverse events

Exclusion Criteria:

- Received >=2 doses of PPV23 prior to study enrollment.

- Living non-independently in an institutional setting, such as a nursing home. Persons
living independently in adult residence communities will be eligible.

- Use of any investigational vaccine within the past 30 days or planned use during the
study period.

- Current or planned participation in a research study of an investigational drug.
Participation in research studies that involve use of licensed drugs, for either
approved or investigational indications, will be permitted with the approval of the
site PI, as will participation in research studies that do not involve medications.

- Current use or previous chronic administration, defined as >=14 days during the
previous six months, of immunosuppressants or other immune-modifying drugs. (For oral
or injected corticosteroids, the immune-modifying dose is defined as prednisone or its
equivalent >=10 mg/day). Topical steroids are allowed.

- Current use of high doses of inhaled steroids, defined as per Table 3.

- Use of cytotoxic therapy in the previous 5 years.

- Plans to receive cytotoxic therapy during the study period.

- Receipt of parenteral immunoglobulin or blood products within three months of study.

- Plans to receive parenteral immunoglobulin or blood products within the study period.

- Current ongoing use of warfarin or heparin or has a bleeding disorder, such as ITP.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, including
human immunodeficiency virus (HIV) infection.

- Anatomic or known functional asplenia.

- History of a hematologic malignancy or a pre-malignant condition (i.e., leukemia,
lymphoma, multiple myeloma, myelodysplasia).

- Active neoplastic disease, excluding local skin cancer or other malignancies (e.g.
prostate cancer) that are stable in the absence of immunosuppressive/cytotoxic or
radiation therapy.

- End-stage liver disease or hepatic failure (as diagnosed by a physician or evidenced
by a history within the last 10 years of bleeding esophageal varices, ascites, or
hepatic encephalopathy).

- Renal failure, as evidenced by current or expected dialysis or known creatinine of
>=2.5 ug/ml.

- Known hypersensitivity to PPV23 or to any component of PPV23 or PCV7, including
aluminum phosphate or diphtheria protein.

- Presence of any other condition or impairment that in the opinion of the investigator
is likely to compromise the participant's ability to complete the study procedures.