Effect of previous vaccination with pneumococcal conjugate vaccine on pneumococcal polysaccharide vaccine antibody responses

Abstract

During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced.

Keywords: pneumococcal conjugate vaccine; polysaccharide antibody deficiency; specific antibody deficiency; unconjugated pneumococcal polysaccharide vaccine.

Figure 1

Box‐plot showing pre‐ [left] and post‐vaccination [middle] pneumococcal antibody concentrations as well as fold‐increase of antibody level (post‐ over prevaccination) (right) for four groups based on age and time of pneumococcal antibody testing. Only 2–5‐year‐old children tested in 2010–12 were vaccinated with PCV‐7 (grey box‐plot). The results are shown for serotype 3 (a) (not included in PCV‐7), serotype 9N (b) (not included in PCV‐7) and serotype 4 (c) (included in PCV‐7). *P‐value between 0·01 and 0·05; **P‐value between 0·001 and 0·01; ***P‐value < 0·001. Median (horizontal line) and quartiles (box) are shown.

Figure 2

Box‐plot showing pre‐ and post‐vaccination serotype‐specific immunoglobulin (Ig)G levels and fold‐increase for non‐PCV‐7 serotype 8 (a), non‐PCV‐7 serotype 19A (b) and PCV‐7 serotype 18C (c). Only 2–5‐year‐old children tested in 2010–12 were vaccinated with PCV‐7 (grey box‐plot). *P‐value between 0·01 and 0·05; **P‐value between 0·001 and 0·01; ***P‐value < 0·001. Median (horizontal line) and quartiles (box) are shown.

Figure 3

Box‐plot showing pre‐ and post‐vaccination serotype 4‐specific IgM (a) and immunoglobulin (Ig)G2 levels (bB) as well as fold increase. Only 2–5‐year‐old children tested in 2010–12 were vaccinated with PCV‐7 (grey box‐plot). *P‐value between 0·01 and 0·05; **P‐value between 0·001 and 0·01; ***P‐value < 0·001. Median (horizontal line) and quartiles (box) are shown.