Vaccination is the most effective way of preventing infectious diseases. Despite the success of vaccines in general, vaccines induce diminished antibody responses and lower protection in the elderly in particular. This could be explained by a defect in the early responses of an ageing immune system. A better understanding of the basic immunological mechanisms that mediate vaccine efficacy is incomplete. Such information is critical and could greatly decrease both the cost and the time to new vaccine development particularly for the geriatric population.

In this trial, the investigators will study the immunologic differences of two FDA approved licensed pneumococcal vaccines between a younger and an older group. Twenty two healthy volunteers between the age of 25-40 and sixty six healthy volunteers between the ages of 60-89 will be enrolled in the study. Each participant in the study will be given one pneumococcal shot. Blood work will be obtained prior to vaccination, one day, three days, seven days, fourteen days, as well as one month and six months after vaccination. Throughout the duration of the study, the participants will be monitored for safety.

RATIONALE: PCV13 [13-valent pneumococcal conjugate vaccine (Prevnar®13)] induces better functional immune responses when compared to PPV23 [23-valent pneumococcal polysaccharide vaccine (Pneumovax®23)] in older naïve adults. We hypothesize that this is due to intrinsic defects in innate responses that could explain the poor immunogenicity of PPV23 when compared to PCV13. Therefore, we propose to extensively study innate and adaptive immune responses generated after administration of either pneumococcal polysaccharide or conjugate vaccines in older adults.

STUDY DESIGN: Single center, open label study in which adult healthy volunteers will be vaccinated with either PPV23 or PCV13. Blood samples will be collected on Days D0 (at enrollment) and D1, D3, D7, D14, D30 and D180 post vaccination to study innate and adaptive immune responses.

Even though PPV23 and PCV13 are considered safe, volunteers will be asked to report any local or systemic AEs from Day 0 (vaccination) to Day 7 . Reactogenicity events will also be evaluated by injection site examination on visits at D0, D1, D3 and D7. Also volunteers are asked to report any local or systemic AEs for 30 days post vaccination and any SAEs for 180 days post vaccination. Volunteers are also asked to report local and systemic AEs developing the day of a blood draw.

Inclusion Criteria:

1. Able to understand and give informed consent.
2. Immunocompetent community dwelling subjects between the ages of ages of 25-40 and 60-89 years.

Exclusion Criteria:

1. Prior vaccination with pneumococcal vaccine.

2. Receipt of any of the following products:

   1. Blood products within 3 months prior to study entry or expected receipt at any time after study entry*.
   2. Any live virus vaccines within 4 weeks prior to study entry or expected receipt within 4 weeks after study entry*.
   3. Any inactivated vaccine within 2 weeks or expected receipt within 2 weeks after study entry*.

3. Presence of co-morbidities or immunosuppressive states such as:

   • Chronic medical problems including (but not limited to) insulin dependent diabetes, severe heart disease, severe lung disease, severe liver disease, cerebrospinal fluid leaks, severe kidney disease, autoimmune diseases, severe gastrointestinal diseases and grade 4 hypertension per CTCAE criteria** .
   • Alcohol, drug abuse or 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 known chronic infections including, but not limited, to known HIV, hepatitis B or C; organ transplant; immunosuppression due to cancer; current and/or expected receipt of chemotherapy, radiation therapy, steroids*** (i.e., more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 90 days , or high dose inhaled corticosteroids**** or any other immunosuppressive therapies (including anti-TNF therapy), functional or anatomic asplenia and congenital immunodeficiency.

4. Conditions that could affect the safety of the volunteers such as:

   o Severe reactions to prior vaccinations.

   o An allergy to any component of the study vaccines (phenol, aluminum, CRM197 protein, succinic acid, Polysorbate 80).

   • History of Guillain-Barré syndrome.
   • History of bleeding disorders.

5. Volunteers with any acute illness* including, but not limited to, - fever (> 100.4 F [> 38 C], regardless of the route) within 3 days prior to study entry.

6. Volunteers with social conditions or occupational conditions or any condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.

7. Pregnant or breast feeding or women expected to conceive within 30 days after vaccination *****

   • 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 reconsidered for enrollment once the condition has resolved as long as the subject continues to meet all other entry criteria.

     • Grade 4 hypertension per CTCAE criteria is defined as Life threatening consequences(e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis) urgent intervention indicated. ***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.

       • High dose ICS is defined as: > 960 mcg/day of beclomethasone dipropionate or equivalent ***** 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, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for 30 days before and 30 days after receiving PPV23 or PCV13.

6 months follow up (started at baseline)