Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine.

OBJECTIVE: To determine whether children with recurrent respiratory infections who failed to respond to the conventional polysaccharide vaccine would respond to a pneumococcal conjugate vaccine. METHODS: Children referred to our clinic for recurrent respiratory infections who had no known primary or secondary immunodeficiencies were immunized with a 23-valent pneumococcal polysaccharide vaccine. IgG antibodies to pneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme-linked immunosorbent assay before and 4 to 6 weeks after immunization. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer > or =1.3 microg/ml or at least 4 times the preimmunization value. Immunization with an experimental CRM197-heptavalent pneumococcal conjugate vaccine was offered to patients without an adequate response to 4 or more vaccine serotypes (nonresponders). Post-conjugate immunization antibody concentrations were measured 4 to 6 weeks later. RESULTS: In nonresponder patients (n = 17) geometric mean post-conjugate immunization (C) serum antibody concentrations (microg/ml) compared with post-polysaccharide (PS) concentrations were: (serotype, C vs. PS) 4, 1.11 vs. 0.30 (P = 0.000227); 6B, 0.46 vs. 0.20 (P = 0.017267); 9V, 0.82 vs. 0.29 (P = 0.002163); 14, 1.88 vs. 0.27 (P = 0.000615); 18C, 0.98 vs. 0.32 (P = 0.021962); 19F, 1.24 vs. 0.34 (P = 0.002844); and 23F, 0.87 vs. 0.16 (P = 0.000194). In responder patients (n = 67), after 1 dose of the polysaccharide vaccine, geometric mean antibody concentrations were: 4, 1.05; 6B, 0.96; 9V, 1.55; 14, 1.65; 18C, 1.62; 19F, 1.30; and 23F, 1.02. CONCLUSIONS: Our results show that a pneumococcal conjugate vaccine is capable of inducing an IgG response in patients with recurrent infections who had failed to mount an adequate response to the polysaccharide vaccine. Conjugate vaccines may be of value in the management of children with recurrent pneumococcal respiratory infections.

Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immunoglobulin concentrations.

BACKGROUND: A deficient antibody response to polysaccharide antigens is determined by measuring the response to the 23-valent pneumococcal polysaccharide vaccine. However, the diagnosis of this specific antibody deficiency is hampered by the lack of sufficient data and standardized testing of the response to pneumococcal polysaccharides. METHODS: All patients evaluated in our allergy/immunology clinic for recurrent respiratory infections between 1995 and 1997 without immunoglobulin, IgG subclass, or other known primary or secondary immunodeficiency were included in this analysis. IgG antipneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F, and 23F were determined by a modified ELISA protocol. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer of 1.3 microg/ml or greater or at least four times the baseline value. RESULTS: A total of 113 patients fulfilling the criteria for inclusion in this analysis were divided into five age groups. The geometric means for preimmunization and postimmunization pneumococcal antibody titers for all serotypes increased with age. For post-immunization antibody concentrations, there was a sharp increase in the specific antibody concentrations in adults in comparison with all pediatric age groups ranging in age from 7 months to 16 years. Similarly, the number of serotypes to which there was an adequate response also increased with age. CONCLUSION: We conclude that the definition of what constitutes an adequate response to pneumococcal immunization needs further definition. It is clear, however, that age has an important influence on the intensity of the response to most pneumococcal polysaccharides. Correlation studies between antibody concentrations in different IgG subclasses, functional studies, and protection studies against mucosal and invasive pneumococcal infections are in progress, and these should contribute to a refined definition of a normal response. The availability of a standardized method for the measurement of IgG antibodies against relevant pneumococcal serotypes is an important step toward this goal.