PCV is more immunogenic than PPV, and induces long\term protection by inducing a memory IgG response 11, 12. 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 SFRP2 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 Introduction Patients with a specific polysaccharide antibody deficiency (SAD) suffer from recurrent respiratory tract infections (sinusitis, otitis, bronchitis or pneumonia) with encapsulated bacteria (e.g. are almost exclusively of the IgG2 subclass, whereas IgG responses after PCV are of the IgG1 subclass 9, 10. PCV is more immunogenic than PPV, and induces long\term protection by inducing a memory IgG response 11, 12. An influence of previous vaccination with PCV on the magnitude and nature of the antibody response to PPV can be suspected. In 33 children with SAD, previous PCV vaccination led to a higher and faster antibody response to PPVCPCV shared serotypes 4, 6B, Veledimex 9V, 14, 18C, 19F and 23F, but not to serotype 5, not contained in PCV 12. In contrast, in HIV\infected adults polysaccharide responsiveness was not biased by prior PCV vaccination 13. The extent to which previous vaccination with a conjugated vaccine affects serotype\specific responses to PPV remains uncertain 14. The aim of this study was to evaluate the effect of previous PCV vaccination on serotype\specific antibody response to subsequent vaccination with PPV. The findings will be important to adapt practice guidelines for SAD diagnosis in patients who have been vaccinated with PCV prior to diagnostic PPV vaccination. The antibody response to PPV was studied retrospectively in a large cohort of patients who underwent diagnostic pneumococcal antibody testing in the context of suspected immunodeficiency. A group aged 2C5 years, tested between 2010 and 2012 and vaccinated with PCV\7 as part of the standard vaccination programme, was compared to a group with the same age, tested between 1998 and 2005, and thus not vaccinated with PCV\7. Patients of 10 years and older, tested for PPV antibody response during these same time\periods, but not vaccinated with PCV\7, served as control populations to exclude confounding factors. Patients and methods Patients All consecutive patients, aged 2C5 years or 10 years and older, tested for antibody response to PPV at the University Hospitals Leuven clinical laboratory from January 1998 to December 2005 and from January 2010 to December 2012, were identified retrospectively. All patients in whom paired pre\ and post\vaccination\specific IgG for serotypes 3, 4 and 9N had been determined were included Veledimex into the study, independent of clinical status or immunocompetence. The study population was divided into four groups, based on age (2C5 ?10 years) and time of pneumococcal antibody response testing (1998C2005 2010C12) (Table 1). The 7\valent PCV (Prevenar?) vaccination was introduced in Belgium in 2004. As a consequence, children aged 2C5 years and tested in 2010C12 (test]. 2010C12?10 yearstest]. 2010C1210C18 yearsmultiple comparison test. The threshold of significance was set at a and/or cross\reactivity. Rose et al. also found a higher percentage of responders to non\PCV serotype 5 in a PCV\primed group than in an unprimed group, although post\vaccination antibody levels to serotype 5 did not differ between a primed and an unprimed group 12. To our knowledge, cross\reactivity of polysaccharide\specific antibodies with serotype 9N or 3 has not been described. However, a conjugate vaccine can increase antibody avidity, thereby increasing cross\reactivity to closely related pneumococcal serotypes 23, 24, 25. Genetic similarity of the encoding regions for different capsular polysaccharides does not predict cross\reactivity between serotypes. For example, serotypes 9N and Veledimex Veledimex 9V were classified historically as one serogroup by their pattern of seroreactivity, but they differ significantly at the genetic level 26. Serotypes 19A and 19F are genetically very similar but, although higher 19A antibodies may be elicited after PCV\7 vaccination (some formulations), cross\reactive antibodies induced by serotype 19F provide limited protection against 19A disease 27, 28. As expected, post\vaccination serotype.
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