Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease

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. ScanlonSteven M. Scharf, Frank C. Sciurba, George R. Washko, Prescott G. Woodruff, Stephen C. Lazarus

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e35-e44
JournalClinical Infectious Diseases
Volume55
Issue number5
DOIs
StatePublished - Sep 1 2012

Bibliographical note

Funding Information:
cal Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the National Heart, Lung, and Blood Institute.

Funding Information:
Potential conflicts of interest. M. T. D. has served as an advisory board member for GlaxoSmithKline and Boehringer Ingelheim and has received industry contracts for clinical trials from GlaxoSmithKline, Boehringer Ingelheim, Otsuka, Boston Scientific and Centocor. R. C. has served in the speakers’ bureau for Pfizer Pharmaceuticals. M. K. H. has participated in advisory boards for Boehringer Ingelheim GmbH, Pfizer, Glaxo-SmithKline, Genentech, Novartis, and Medimmune; has participated on speaker’s bureaus for Boehringer Ingelheim GmbH, Pfizer, GlaxoSmith-Kline, the National Association for Continuing Education, and WebMD; has consulted for Novartis and Nycomed; and has received royalties from UpToDate and ePocrates. B. M. has served on an advisory boards for Merck and Pfizer and has been the local principal investigator for multicenter trials sponsored by Pfizer. F. J. M. has participated in Advisory Boards in COPD development for Actelion, Astra Zeneca, Bayer, Boom-Comm, fbCommunications, Forest/Almirall, GSK, Ikaria, MedImmune, Merck, Novartis, Nycomed, Pearl, Pfizer, Roche, Schering, and Talecris; has been a member of Steering Committee for COPD studies sponsored by Actelion, GSK, Forest, MPex, and Nycomed; has participated in FDA Mock panels for Boehringer Ingelheim and Forest; has served on speaker’s bureaus or in CME activities sponsored by American Lung Association, Almirall, Altana/Nycomed, Astra Zeneca, Boehringer Ingelheim, CME Incite, ePocrates, Forest, France Foundation, GSK, MedEd, NACE, Pfizer, Potomac, Prescott, Sanofi Aventis, Vox Medic, WebMD, and UpToDate; and has received royalties from Associates in Medical Marketing, Castle Connolly. D. E. N has received advisory fees from Merck and Pfizer. P. D, S. has participated in clinical trials funded by Pfizer and Boehringer Ingel-heim, and his wife works for Merck Research Laboratories. P. G. W. has had a recent research grant with Genentech, recent consulting for Medi-mmune, and is co-inventor on a patent pending for asthma diagnostics. The University of Alabama at Birmingham owns the intellectual property rights to some of the reagents described in this work. M. H. N., R. L. B., W. C. B., J. A. D. C. and M. T. D. are employees of the University of Alabama at Birmingham, and M. H. N. has been a consultant to Merck regarding the diagnosis of pneumonia. All other authors report no potential conflicts.

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