Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia

Abstract

Background: Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia.

Methods: Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination.

Results: PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels.

Conclusions: In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.

Figure 1

IgG to capsular polysaccharides (in µg/ml) is shown for Group 1 (patients who received PPV followed, 6 months later, by PCV, dashed lines) and Group 2 (patients who received PCV followed, 6 months later, by PPV, solid lines). Each panel shows results for a different CPS.

Figure 2

Opsonic activity reported as OPK index for four CPS at each point of the study. Group 1 (PPV followed by PCV) is shown by dashed lines and Group 2 (PCV followed by PPV) by solid lines.

Figure 3

IgG after patients received PPV followed by PCV (Panel A) or vice-versa (Panel B), with patients stratified according to prior vaccination status. Dotted line: those who received pneumococcal polysaccharide vaccine within the previous year; dashed line: those vaccinated 1 – 5 years previously; and solid line: those vaccinated > 5 years previously or never vaccinated. Representative data are shown for CPS 6B; similar responses were observed with the other 3 CPS studied. None of the patients in Group 1, who received PPV in the previous year (Panel A) had a 6 month follow-up serum. Small numbers of subjects in some groups precluded statistical analysis.