Immunogenicity after one,two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto,South Africa

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 CRM(197) mutant 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 microg/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 microg/ml for serotype 23F to 2.98 microg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 microg/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 microg/ml for serotype 23F to 5.68 microg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 microg/ml and >75% had >0.5 microg/ml for all nine serotypes. GMCs after three doses ranged from 2.73 microg/ml for serotype 23F to 6.18 microg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 microg/ml and >92% had >0.5 microg/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type 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.