56 EU, Pakistan GM = 0.53 EU; p = 0.8327) and so unlikely to explain the lack of association with birth weight observed in the current study. Relative differences in relation to the pneumococcal vaccine cannot be compared since this vaccine was not used in the study in Pakistan. In the current study we observed an interesting effect of a number of contemporaneous measures and antibody response to both vaccines. When combined in multiple regression analyses, the measures shown to have the most significant effects were serum neopterin

and plasma leptin levels, and pre-vaccination antibody titres. Neopterin is a macrophage-derived protein commonly used as a marker of immune activation, and elevated levels of peripheral blood neopterin indicate an unregulated cellular immune Ibrutinib chemical structure response. In the current PI3K inhibitor cancer study, serum levels of neopterin independently and positively predicted antibody response to serotypes 1 and 5 of the pneumococcal vaccine, but not to serotypes 14 and 23F or the response to the Vi vaccine. Although it is difficult to explain why individuals with elevated immune activation responded more effectively to these two serotypes only, we speculate that an enhanced vaccine response in subjects could be the result of a co-stimulatory effect of an already elevated state of immune activation.

Whether such an effect has any longer term implication on antibody titres, remains to be determined. Leptin, a primarily adipocyte-derived hormone, was positively correlated with serotype 14 of the pneumococcal vaccine but not with the response to any other serotypes or the Vi vaccine. Leptin levels correlate with body fat mass and leptin has more recently been implicated as a central mediator connecting nutrition to immunity [2]. Data from animal models have suggested

that leptin may mediate the effects of malnutrition on T cell function [31] and [32], although little data currently exists to suggest that these effects translate into compromised specific immune responses in malnourished humans (e.g. [33]). see more Further work may be warranted to help understand the specific relationship between plasma leptin levels and antibody response to serotype 14 of the pneumococcal vaccine. With the exception of antibody response to serotype 23F of the pneumococcal vaccine, a highly significant effect of pre-vaccination antibody levels on post-vaccination titres was observed for both vaccines. Pre-vaccination antibody titres are a consequence of previous exposure to the vaccine antigens; for pneumococcal serotypes this is mainly via exposure to the same or similar serotypes encountered during nasopharyngeal carriage. A longitudinal study of households in the UK showed strong immune response to the carriage serotype, supporting the assumption that natural immunity to Streptococcus pneumoniae is induced by exposure to S. pneumoniae [34].