Mink, S. dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the DL-Carnitine hydrochloride ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults. is a major respiratory pathogen of toddlers and elderly adults, causing 1 million childhood deaths per year worldwide (19). The peak incidence of invasive pneumococcal disease is between 4 and 18 months, when maternal antibody has waned and before the immune responsiveness to polysaccharide antigens develops (59). The introduction of a new heptavalent, conjugated pneumococcal capsular polysaccharide vaccine (Pnc7) in the United States in 2000 led to a major reduction in invasive pneumococcal disease cases among immunized toddlers (7, 79) and more widely in the population as a result of herd immunity, which arises because of the reduced transmission of the organism through the blockage of nasopharyngeal carriage (32, 41, DL-Carnitine hydrochloride 45, 78). Toddlers immunized at 2, 4, and 6 months of age generate immunoglobulin G (IgG) antibody responses to Pnc7 (16), but the serum antibody wanes rapidly, with some serotype-specific antibody levels falling below the protective threshold within a matter of months (47, 64). Similarly, in early infancy antibody wanes rapidly after immunization with other glycoconjugate vaccines, such as the type b (30) and serogroup C glycoconjugate vaccines (68), and there is a corresponding loss of vaccine effectiveness (56, 70). This failure of persistence of IgG to capsular polysaccharides after immunization in infancy may be overcome by the subsequent administration of a booster dose of a conjugate vaccine at 12 to 15 months of age, which results in a marked rise in IgG antibody levels, demonstrating that immunological memory had been induced by priming (2, 3, 58). In the United Kingdom, Pnc7 was introduced into the primary DL-Carnitine hydrochloride immunization schedule at the end of 2006 as two doses given at 2 months and 4 months of age, with a booster dose given at 13 months of age. Children between 12 months and 2 years of age at the time that Pnc7 was introduced were included in a single-dose catch-up campaign. However, at 12 months of age, a single dose of Pnc7 may not be sufficient to induce protective levels (a protective level has been variously described as >0.2 g/ml or as 0.35 g/ml or 1.0 g/ml [4, 27]) of antibodies to all seven serotypes included in the current vaccine (47), and there is little information about the persistence of antibody after this single-dose priming regimen and the subsequent memory responses. By contrast, in adults a single dose of Pnc7 is sufficient to induce protective levels of IgG to all seven serotypes included in Pnc7, although the levels also wane somewhat (1, 33, 62, 80) and no further increase in response is demonstrated following reimmunization (75), perhaps because the polysaccharide antigens (conjugated as well as purified) stimulate predominantly marginal zone B (MZB)-cell responses in this age group (9, 37, 74, 75). These cells accumulate with age and require a mature splenic marginal zone to function. They are also capable of rapid isotype switching to IgG positivity during the first week after immunization (21). Thus, fewer of these cells in early infancy and the immature phenotype expressed by these cells may also contribute to the lack Rabbit Polyclonal to SHC3 of the long-term maintenance of serum IgG levels in toddlers (81). During the first 7 days of the immune response to a booster dose of glycoconjugate vaccine there is a rapid but transient rise in the frequency of antigen-specific antibody-forming cells (AFCs) in the peripheral blood of adults by DL-Carnitine hydrochloride day 7 (12). These cells disappear from the circulation by day 9 of the vaccine response. A similar time course has also been reported in response to plain pneumococcal polysaccharide vaccines, tetanus DL-Carnitine hydrochloride toxoid, and influenza vaccines (17, 25); and it is likely that these AFCs are plasma cells generated from preexisting memory cells. However, various subsets of B cells.