Leach, and D. 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants. Every year approximately 1 million children under 5 years of age die of pneumococcal pneumonia, meningitis, or sepsis, mostly in developing countries (4). Despite the efficacy of pneumococcal conjugate vaccines, remains an important cause of serious morbidity and mortality in young infants in developing countries (5, 8, 44), where the age of onset of disease is usually often younger than the recommended vaccination age of 6 weeks aged and many of the serotypes causing serious disease are not included in currently available conjugate vaccines. Alternative vaccines and vaccine strategies are therefore needed to induce the earliest protection possible in high-risk infants. Early onset of pneumococcal colonization and prolonged carriage in the upper respiratory tract are believed to play important functions in the high incidence and early onset of RWJ-51204 pneumococcal diseases in children in developing countries (10, 25). In the highlands of Papua New Guinea (PNG), where this study was performed, all infants carry pneumococci in the upper respiratory tract by the age of 3 months aged, and 60% of them are already carriers during the neonatal period at a median age of 17 days aged (14). This is in contrast to high-income countries, where less than half of the children experience pneumococcal colonization within the first 12 months of life (3, 10, 43). Besides children, pneumococcal carriage rates remain higher in adulthood in developing countries, including PNG, where approximately half of the adults carry pneumococci in the upper respiratory tract (17, 39), compared to 1 to 13% of adults in low-risk countries (12, 15, 20). Consequently, maternal pneumococcal carriage may be an RWJ-51204 important risk factor for early colonization in infants in high-risk areas, in particular considering the frequent and close contact between mother and child in the crucial early period of life when infants are highly susceptible. In the first few months of life, when the human immune system is still highly immature (27), infants largely depend on passively acquired maternal immunoglobulin G (IgG) antibodies to protect themselves against invading pathogens. Immunization of pregnant women is a strategy that has been proven to reduce infection risks in both mothers and infants (9, 13, 45). This includes the potential to reduce acute lower respiratory illnesses in infants in high-risk areas, RWJ-51204 as shown with maternal immunization with the 23-valent pneumococcal polysaccharide vaccine (36, 37). However, the efficacy of pneumococcal polysaccharide vaccines on reducing nasopharyngeal colonization is limited, whereas the protective effect of pneumococcal conjugate vaccines is restricted by the number of pneumococcal serotypes that can be included. On the other hand, novel vaccines based on conserved pneumococcal proteins may offer better, serotype-independent protection against pneumococcal carriage and disease. This PRKM12 may include maternal immunization strategies, as supported by findings in mice (21). Pneumolysin (Ply) and pneumococcal surface protein A (PspA) are two conserved proteins that are expressed by virtually all isolates and that are being considered as vaccine candidates. Pneumolysin is the thiol-activated cytolysin produced by that enables the bacterium to penetrate the host’s physical defenses through its cytotoxic effect on epithelial cells, thus facilitating carriage and disease (28). PspA is usually a cell wall-associated protein that plays a role in inhibiting complement-mediated opsonization (7, 33) and can prevent lactoferrin-mediated clearance (19). In contrast to Ply, PspA shows structural diversity between pneumococcal strains and has been classified into three families based on the sequence variability.