The purpose of this study is to learn whether or not giving a tetanus/diphtheria vaccination ("tetanus shot") before giving pneumococcal vaccine makes the pneumococcal vaccine more effective without causing too many side effects.

The only vaccine licensed in the United States for protecting adults against pneumococcal disease (PPV23) protects against invasive disease in observational studies but has generally been poorly effective against pneumonia or all-cause mortality in randomized clinical trials. Another vaccine containing seven polysaccharide antigens conjugated to diphtheria toxoid (PCV7) is licensed for children and under investigation in adults.

In this pilot study, we are comparing the safety and immunogenicity of three immunization schedules in adults:

• Td vaccine, 2-week interval, PCV7, 4-month interval, PPV23
• PCV7, 4-month interval, PPV23
• PPV23

We aim to:

• compare the safety profiles of pneumococcal vaccines given on each of the three schedules
• compare serotype-specific ELISA antibody response to pneumococcal antigens given on each of the three schedules
• compare functional serotype-specific antibody responses to pneumococcal antigens given on each of the three schedules
• study the influence of diphtheria antibody levels at the time of pneumococcal conjugate vaccine administration on the magnitude of the immune response to pneumococcal antigens

Exclusion Criteria:

• Participation in any other investigational clinical trials except purely observational studies within 4 weeks prior to study start
• Any vaccination within 2 weeks prior to first study vaccine
• Evidence of systemic or local infection within one week prior to first study vaccine
• HIV infection
• Renal failure
• Receipt of a pneumococcal or Td vaccine within 5 years
• Current receipt of therapy for neoplastic disease
• Current receipt of immunosuppressive therapy
• Terminal illness withlife expectancy less than 3 months