Immunogenicity and Reactogenicity of Pneumococcal Polysaccharide and Conjugate Vaccines in Native Elders
Condition: Pneumococcal Infections
MeSH terms: Pneumococcal Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      To test the hypothesis that immune responses to 23-valent pneumococcal polysaccharide vaccine
      (PPV-23) could be improved in Alaska Native elders by immune priming with 7-valent
      pneumococcal conjugate vaccine (PCV-7), we assessed post-vaccination immune responses among
      Natives aged 55 years and older who were randomized into three arms: (1) one dose of PPV-23
      according to current state and ACIP recommendations; (2) one dose of PCV-7 followed two
      months later with a dose of PPV-23; and (3) one dose of PCV-7 followed six months later with
      a dose of PPV-23.
    

Detailed description: 
      Rates of invasive pneumococcal infection (bacteremia and meningitis caused by Streptococcus
      pneumoniae) for Alaska Natives are among the highest in the United States and are
      approximately five-fold higher than rates among non-Natives living in Alaska. Disease is most
      common among the very young and the elderly (73 cases/100,000 Natives ≥55 years old)1.
      Case-fatality from pneumococcal infection is highest (>15%) among the elderly. A 23-valent
      pneumococcal polysaccharide vaccine (PPV-23) has been licensed in the United States since
      1983. The CDC Advisory Committee on Immunization Practices (ACIP) recommends vaccination with
      PPV-23 for all Alaska Natives aged two years and older, however the Alaska Department of
      Health and the Alaska Native Tribal Health Consortium only target and fund vaccination for
      those aged 55 years and older. Post-licensure epidemiological studies have documented
      effectiveness of PPV-23 for prevention of invasive infection (bacteremia and meningitis)
      among the elderly and younger adults with certain chronic medical conditions. The overall
      effectiveness against invasive pneumococcal disease among immunocompetent persons age ≥65
      years is 75%; however, efficacy may decrease with advancing age.

      PPV-23 has several limitations. Efficacy of pneumococcal polysaccharide vaccines against the
      most common types of pneumococcal infection in the elderly, bronchitis and pneumonia without
      bacteremia, has not been documented in controlled, randomized trials. Additionally,
      antibodies against pneumococcal polysaccharides decline after immunization and often return
      to pre-vaccination concentrations within 5 years. A case-control study evaluating vaccine
      effectiveness suggests that the decline in antibody concentration is associated with
      declining protection against invasive pneumococcal infection. At present, the Alaska
      Department of Health recommends revaccination with PPV-23 every 6 years. This is in contrast
      to ACIP recommendations for only one revaccination. A retrospective review found similar
      rates of local and systemic reactions among 179 Alaska Native elders who received a third
      dose of PPV-23 compared to 180 receiving a first or second dose. Although available data
      suggest that revaccination with PPV-23 is safe, clinical benefits of revaccination are
      unproven. T-cell independent antigens, such as polysaccharides, do not produce booster
      responses to revaccination, and antibody levels after revaccination do not exceed those after
      primary immunization.

      A 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in 2000 (Prevnar™, Wyeth
      Lederle Vaccines) for prevention of invasive pneumococcal disease in infants and young
      children. This vaccine was safe and effective for prevention of invasive pneumococcal disease
      in a large randomized trial conducted among infants aged two months and older enrolled in a
      northern California HMO. The role of pneumococcal conjugate vaccines among adults has not
      been defined. Potential advantages of conjugate vaccines compared to PPV-23 include the
      T-cell dependent immune response to conjugate vaccines which lead to immunologic memory and
      booster responses characterized by rapid and dramatic increases in antibody after
      revaccination. PCV-7 should also overcome the limitations of the poorly immunogenic antigens
      in PPV-23, including those resistant to antimicrobial drugs. An additional potential
      advantage of PCV-7 is greater mucosal immunity with possible protection against
      non-bacteremic pneumococcal respiratory tract infections-a benefit that has never been
      confirmed for PPV-23 among the elderly. Potential disadvantages of PCV-7 in adults include
      limited serotype coverage. Only 50% of invasive pneumococcal infections in Alaska Natives
      aged 55 and older are caused by the seven serotypes included in PCV-7 compared to more than
      90% for PPV-23. Preliminary data from studies of healthy persons ≥50 years old and of
      patients vaccinated after treatment for Hodgkin's disease indicate that antibody responses to
      a dose of pneumococcal conjugate vaccine have not been substantially better than responses to
      PPV-23. One approach to the use of conjugate vaccines in adults is to administer conjugate
      vaccine to prime the immune system and to subsequently give a dose of PPV-23 to induce a
      booster response to the serotypes present in both vaccines as well as primary T-cell
      independent responses to the serotypes in PPV-23 only. Immunogenicity studies have documented
      boosting with polysaccharide vaccine in children with chronic illnesses and in adults with
      Hodgkin's Disease after primary vaccination with pneumococcal conjugate vaccine. However,
      there are no published data evaluating this strategy for preventing pneumococcal disease in
      the elderly, and no data are available for Alaska Natives.

      We studied the immunogenicity of PCV-7 in Alaska Native elders. Participants were randomized
      into three arms: (1) one dose of PPV-23 according to current state and ACIP recommendations;
      (2) one dose of PCV-7 followed two months later with a dose of PPV-23; and (3) one dose of
      PCV-7 followed six months later with a dose of PPV-23. Immune responses for all conjugate
      vaccine pneumococcal serotypes will be determined by enzyme linked immunosorbent assay
      (ELISA) and antibody affinity at the Centers for Disease Control and Prevention's (CDC)
      Arctic Investigations Program (AIP) laboratory located on the Alaska Native Medical Center
      (ANMC) campus.
    

Intervention name(s): Pneumococcal polysaccharide vaccine; Pneumococcal conjugate vaccine
Intervention type(s): Biological; Biological
Intervention MeSH terms: Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention