Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

Clinical Infectious Diseases, Sep 2012

Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977.

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Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

Mark T. Dransfield () 0 7 8 Sarah Harnden 0 6 Robert L. Burton 0 13 Richard K. Albert 0 12 William C. Bailey 0 8 Richard Casaburi 0 11 John Connett 0 6 J. Allen D. Cooper 0 Jr 0 7 8 Gerard J. Criner 0 10 Jeffrey L. Curtis 0 15 MeiLan K. Han 0 15 Barry Make 0 14 Nathaniel Marchetti 0 10 Fernando J. Martinez 0 15 Charlene McEvoy 0 9 Moon H. Nahm 0 13 Dennis E. Niewoehner 0 9 Janos Porszasz 0 11 John Reilly 0 4 Paul D. Scanlon 0 5 Steven M. Scharf 0 2 Frank C. Sciurba 0 4 George R. Washko 0 3 Prescott G. Woodruff 0 1 Stephen C. Lazarus 0 1 for the NIH COPD Clinical Research Network 0 0 Received 24 February 2012; accepted 15 May 2012; electronically published 31 May 2012. Care, University of Alabama at Birmingham and the Birmingham VA Medical Center, 422 THT 1900 University Blvd , Birmingham, AL 35294 1 Division of Pulmonary and Critical Care Medicine and Cardiovascular Research Institute, University of California , San Francisco 2 Division of Pulmonary and Critical Care Medicine, University of Maryland , Baltimore 3 Division of Pulmonary & Critical Care Medicine, Brigham & Women's Hospital , Boston, Massachusetts 4 Division of Pulmonary and Critical Care Medicine, University of Pittsburgh , Pennsylvania 5 Division of Pulmonary and Critical Care Medicine, Mayo Clinic , Rochester, Minnesota 6 Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis 7 Pulmonary Section, Birmingham VA Medical Center , Alabama 8 Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham 9 Pulmonary Section, University of Minnesota VA Medical Center , Minneapolis 10 Division of Pulmonary and Critical Care Medicine, Temple University , Philadelphia, Pennsylvania 11 Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center , Torrance, California 12 Department of Medicine, Denver Health Medical Center , Colorado 13 Departments of Pathology and Microbiology, University of Alabama at Birmingham 14 National Jewish Health, University of Colorado , Denver 15 Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. - Streptococcus pneumoniae is a major cause of pneumonia, hospitalization, and mortality and disproportionately affects those with comorbid illnesses, such as chronic obstructive pulmonary disease (COPD) [1]. Until recently, the only pneumococcal vaccine approved for use in adults in the United States and Europe was the 23-valent pneumococcal polysaccharide vaccine (PPSV23) [2]. Although PPSV23 provides partial protection against invasive pneumococcal disease in young healthy patients, it appears to have limited impact on this risk among older patients and those with underlying medical problems [3]. In addition, the benefit of PPSV23 on the incidence of nonbacteremic pneumonia has not been clearly demonstrated [2, 4], and no randomized, controlled trial of the vaccine in patients with COPD has shown a reduction in clinical outcomes in the intention-to-treat population [59]. Although observational studies suggest that PPSV23 offers some protection against pneumococcal infection in patients with l (...truncated)


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Mark T. Dransfield, Sarah Harnden, Robert L. Burton, Richard K. Albert, William C. Bailey, Richard Casaburi, John Connett, J. Allen D. Cooper, Gerard J. Criner, Jeffrey L. Curtis, MeiLan K. Han, Barry Make, Nathaniel Marchetti, Fernando J. Martinez, Charlene McEvoy, Moon H. Nahm, Dennis E. Niewoehner, Janos Porszasz, John Reilly, Paul D. Scanlon, Steven M. Scharf, Frank C. Sciurba, George R. Washko, Prescott G. Woodruff, Stephen C. Lazarus, for the NIH COPD Clinical Research Network. Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease, Clinical Infectious Diseases, 2012, pp. e35-e44, 55/5, DOI: 10.1093/cid/cis513