Superior immune response to protein-conjugate versus free pneumococcal polysaccharide vaccine in chronic obstructive pulmonary disease

Mark T. Dransfield, Moon H. Nahm, MeiLan K. Han, Sarah Harnden, Gerard J. Criner, Fernando J. Martinez, Paul D. Scanlon, Prescott G. Woodruff, George R. Washko, John E. Connett, Nicholas R. Anthonisen, William C. Bailey

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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 (NCT00457977).

Original languageEnglish (US)
Pages (from-to)499-505
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number6
StatePublished - Sep 15 2009

Bibliographical note

Funding Information:
We are grateful to the families who have participated in this study. We thank Erica Fong for helping us with AB3700 sequencing in the Core Laboratories of the Center for Human Genetics and Integrative Biology at the University of Pittsburgh. We also thank Dr. Robert E. Ferrell for aiding us with our control samples. This research was supported by National Institutes of Health (NIH) grant EY13130 (to M.B.G.); by NIH Core Grant for Vision Research EY08098; by the Eye and Ear Foundation of Pittsburgh (support to M.B.G.); by Fight For Sight, the Research Division of Prevent Blindness America (support to F.Y.K.D.); and by Research to Prevent Blindness, New York.


  • COPD
  • Immune responses
  • Immunization
  • Pneumococcal vaccines
  • Vaccination


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