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

Abstract

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 www.clinicaltrials.gov (NCT00457977).

Figures

Figure 1.

The serotype-specific baseline and 1-month opsonophagocytosis killing index (OPK) are shown for each patient. The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) resulted in statistically significantly higher 1 month to baseline OPK ratios for serotypes 4 (75.5 [95% confidence interval, 43.9–130] vs. 10.3 [6.1–17.6]; P < 0.001), 9V (18.7 [10.3–34.0] vs. 5.7 [3.6–9.2]; P = 0.003), 18C (31.3 [16.2–60.4] vs. 9.5 [5.7–16.1]; P = 0.006), 23F (52.4 [26.2–104] vs. 7.2 [4.1–12.7]; P < 0.001). PCV7 vaccination elicited a nonstatistically significant but superior response for serotypes 6B (20.8 [11.3–38.1] vs. 11.2 [6.3–19.88]; P = 0.09) and 14 (22.8 [9.9–52.2] vs. 10.7 [5.8–19.8]; P = 0.24), whereas 23-valent pneumococcal polysaccharide vaccine (PPSV23) elicited a similar improved response for serotype 19F (20.65 [11.05–38.61] vs. 10.6 [5.5–20.4]; P = 0.20). Horizontal bars indicate geometric mean OPK.

Figure 2.

Shown are the serotype-specific baseline and 1-month opsonophagocytosis killing index (OPK) for the four most frequently recovered pneumococcal serotypes in patients with chronic obstructive pulmonary disease (27) divided by prior vaccination status and vaccine assignment. The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) elicited statistically superior 1 month to baseline OPK ratios compared with PPSV23 in vaccine-naive subjects for serotypes 9V (P = 0.04), 14 (P = 0.006), and 23F (P < 0.001). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) elicited a superior response for serotype 19F (P = 0.05). Among previously vaccinated subjects, PCV7 elicited superior OPK ratios for serotypes 9V (P = 0.01) and 23F (P = 0.05). There was no statistical difference in OPK responses for serotype 14 (P = 0.22) and 19F (P = 0.94). Horizontal bars indicate geometric mean OPK.