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Superior Immune Response to Protein-Conjugate versus Free Pneumococcal Polysaccharide Vaccine in Chronic Obstructive Pulmonary Disease

¹ Division of Pulmonary, Allergy and Critical Care Medicine and ² Departments of Pathology and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, ³ Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, Michigan, ⁴ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, ⁵ Pulmonary and Critical Care Medicine and Temple Lung Center, Temple University, Philadelphia, Pennsylvania, ⁶ Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, ⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California, ⁸ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham & Women's Hospital, Boston, Massachusetts, and ⁹ Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Correspondence and requests for reprints should be addressed to Mark Dransfield, M.D., 422 THT, 1900 University Boulevard, Birmingham, AL 3594. E-mail: mdransfield99{at}msn.com

Rationale: Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults.

Objectives: We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD. We also posited that older age and prior PPSV23 vaccination would be associated with reduced vaccine responsiveness.

Methods: One hundred twenty patients with COPD were randomized to PPSV23 (63 subjects) or PCV7 (57 subjects). IgG concentrations were determined by ELISA; functional antibody activity was assayed with a standardized opsonophagocytosis assay and reported as an opsonization killing index (OPK). Increases in serotype-specific IgG and OPK at 1 month post vaccination were compared within and between vaccine groups.

Measurements and Main Results: Both vaccines were well tolerated. Within each study group, postvaccination IgG and OPK were higher than baseline (P < 0.01) for all serotypes. Adjusted for baseline levels, postvaccination IgG was higher in the PCV7 group than the PPSV23 group for all seven serotypes, reaching statistical significance for five (P < 0.05). PCV7 resulted in a higher OPK for six of seven serotypes (statistically greater for four) compared with PPSV23. In multivariate analyses, younger age, vaccine naivety, and receipt of PCV7 were associated with increased OPK responses.

Conclusions: PCV7 induces a superior immune response at 1 month post vaccination compared with PPSV23 in COPD. Older age and prior PPSV23 reduce vaccine responsiveness.

Clinical trial registered with www.clinicaltrials.gov (NCT00457977).

Key Words: pneumococcal vaccines • vaccination, COPD • immune responses • immunization

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Debate remains about the protective efficacy of antibodies produced in response to the 23-valent free pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD) and no study has accurately examined its immunogenicity in this population. Preliminary data suggest that a protein-conjugate pneumococcal vaccine (PCV7) may elicit superior immune responses to PPSV23 in healthy elderly patients. What This Study Adds to the Field PCV7 induces a superior immune response to PPSV23 in COPD at 1 month post vaccination. Both vaccines elicit responses comparable to those previously observed in healthy elderly patients.

 

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