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

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.

• Authors: 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, NIH COPD Clinical Research Network
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 55 Issue 5 Pg. e35-44 (Sep 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22652582 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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