As demonstrated in Table 1, CRM197-IFN-γ responses at age 3 months correlated significantly with antibody titres at 9 months; this confirms the ability of neonatal immunisation to induce functional type-1 immunity. Furthermore, the positive associations between the Th2 response and circulating antibody titres at age 3 months suggest that Th2 responses do not negatively interfere with the induction of immunity, but rather facilitate responses, possibly by driving initial B-cell switching and proliferation. One measure of demonstrating the safety of neonatal vaccination is excluding the possibility of any interference

with cellular immune responses to expanded program of immunisation (EPI) vaccines or with normal maturation of the immune system. We have previously demonstrated that at 3 months of age type-1 and 2 cytokine responses www.selleckchem.com/products/BKM-120.html to the concomitant vaccine antigens PPD (BCG), HbsAg (HepB) and TT (DTwP/Hib), and polyclonal T cell responses to PHA were similar in the 3 study groups [18]. Repeating

this measure at 9 months of age for responses to TT and PHA as well as the later administered measles vaccine (1st dose at 6 months of age), cellular immune responses were again found to be similar in the three groups (except for higher PHA-TNFα responses in the infant than in the neonatal group, p = 0.004) ( Fig. 3). Hospitalization in the first month of life children did not differ between children in high throughput screening assay the neonatal vaccination group (1.3/1000 person days) compared to those who had not received a neonatal dose (3.0/1000

person days) (p = 0.18), indicating that neonatal vaccination did not impose an early health risk. In this study we have shown in human newborns at high risk of pneumococcal disease and death that both neonatal and infant PCV immunisation schedules successfully prime and induce persisting protective immune however responses in these high-risk infants; that neonatal immunisation with PCV induces a similar type-1/type-2 memory response as vaccination starting at the current PNG EPI age of 1 month (which is a bit earlier than most schedules starting at 6 weeks of age in developing countries); and that vaccine-induced Th2 responses do not negatively interfere with the induction of immunity. Our results are in disagreement with mouse studies showing that vaccination in early life induces skewed Th2 responses, with little development of sterilizing Th1 immunity. Although the primary response in neonatal mice appears to compromise both Th1 and Th2 cells [24], Th1 cells appear to undergo apoptosis in response to a secondary challenge while Th2 cells remain responsive [25] and [26]. To date, only a few human studies have reported on the effect of neonatal vaccination on T-cell development.