Background.Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children.Objectives.To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens.Methods.A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n= 250) or 9-valent pneumococcal conjugate vaccine (n= 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM197mutant diphtheria protein. Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose.Results.Before the first dose at 6 weeks of age >80% of infants had >0.15 &mgr;g/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4. Geometric mean concentrations (GMCs) after one dose ranged from 0.27 &mgr;g/ml for serotype 23F to 2.98 &mgr;g/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 &mgr;g/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 &mgr;g/ml for serotype 23F to 5.68 &mgr;g/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 &mgr;g/ml and >75% had >0.5 &mgr;g/ml for all nine serotypes. GMCs after three doses ranged from 2.73 &mgr;g/ml for serotype 23F to 6.18 &mgr;g/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 &mgr;g/ml and >92% had >0.5 &mgr;g/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher toHaemophilus influenzaetype b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls.Conclusions.A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.