Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV. Pneumococcal infections cause at least one million deaths T worldwide annually, mostly in young children (52). Immunization against has the potential to face this burden of disease. An ideal vaccine should rapidly elicit protective immunity and generate memory cells, which respond efficiently to subsequent antigen exposure. Generation of memory B cells and long lived plasma cells is associated with isotype switching and hypermutation of the immunoglobulin genes, resulting in selection of B cells with high-affinity B-cell receptors (27, 28). The established 23-valent pneumococcal polysaccharide vaccine (PPV-23) induces in adults primarily immunoglobulin M (IgM), with hardly any class switching, affinity maturation, or immunological memory (29, 47). It is ineffective in infants and of limited efficacy in high-risk patients, since it elicits a solely T-cell-independent immune response. In 2000, a 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United States, resulting in a dramatic decrease of invasive pneumococcal disease in the following years (8, 51). The efficacy of the conjugate Daptomycin vaccine is due to several mechanisms: increased amounts of circulating antibodies, higher avidity, and an induction of immunological memory (2, 9, 16, 18). In addition, a reduction of nasopharyngeal carriage of pneumococci was described for the PCV-7 (13, 14, 26, 31). In light of the clinical background, the induction of memory appears mandatory for long-term protection against pneumococcal disease. In addition, antibody concentrations gradually diminish after primary series of PPV, and may fall below a Daptomycin protective threshold, underlining the importance of memory versus circulating antibodies. However, while conjugate pneumococcal vaccine apparently confers protection against pneumococci, the presence of polysaccharide specific immunological memory is difficult to demonstrate in individual subjects. Pneumococcal polysaccharide specific memory in subjects immunized with glycoconjugates is demonstrated by challenge with PPV, and the anamnestic response of polysaccharide-specific IgG is considered a surrogate marker for memory (12). Here, we investigated the immunogenicity of PCV with a focus on its ability to induce an anamnestic response in patients with recurrent infections and an inability to respond to PPV immunization sufficiently (55). This so-called polysaccharide-specific immunodeficiency (PSI) is defined as an impaired immune response to polysaccharide antigens, while antibody response to protein antigens is intact. In this regard, PSI is an excellent in vivo model to study the immunogenicity of protein-coupled polysaccharide vaccines such as Daptomycin PCV. Typically, these patients suffer from recurrent respiratory infections, which are mostly due to encapsulated Daptomycin bacteria and require frequent antibiotic treatment (3, 38, 49, 56). An effective vaccine strategy for this patient group is still pending. In such risk groups, immunological memory is a crucial secondary parameter to characterize functional antibody activity and long-term protective responses. In order to study the nature and kinetics of the immune response, we detected pneumococcal antibodies on day 7 after vaccination as early postchallenge samples, and on day 28, representing late response. Additionally, since the host’s protection against pneumococcal infections is mediated mainly by phagocytosis, we also determined the opsonophagocytic activity (OPA).