Immunogenicity and Reactogenicity of Pneumococcal Polysaccharide and Conjugate Vaccines in Native Elders

March 19, 2007 updated by: Centers for Disease Control and Prevention
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

90

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Alaska Native Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 55 to 70 years
  • Alaska Native

Exclusion Criteria:

  • Immune compromising condition
  • Neurological disease
  • Immune suppressive medication or immunoglobulin within 6 months
  • Previous pneumococcal vaccination

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Immune responses

Secondary Outcome Measures

Outcome Measure
Systemic and injection site reactions

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

Southcentral Foundation
Alaska Native Tribal Health Consortium

Investigators

  • Principal Investigator: Karen Miernyk, MS, Alaska Native Tribal Health Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Study Completion

June 1, 2003

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

March 20, 2007

Last Update Submitted That Met QC Criteria

March 19, 2007

Last Verified

September 1, 2005

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCID-3316

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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