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

Clin Infect Dis. 2012 Sep;55(5):e35-44. doi: 10.1093/cid/cis513. Epub 2012 May 31.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Female
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Phagocytosis / immunology
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology*
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / microbiology*

Substances

  • 23-valent pneumococcal capsular polysaccharide vaccine
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Immunoglobulin G
  • Pneumococcal Vaccines

Associated data

  • ClinicalTrials.gov/NCT00457977