Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

Abstract

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 g/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 g/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

Social Mixing with Other Children during Infancy Enhances Antibody Response to a Pneumococcal Conjugate Vaccine in Early Childhood

“…Previous authors have commented that the most common pneumococcal serotypes that cause infections in children are the poorest immunogens in this age group (10,20). The poor immunogenicity of serotype 6B polysaccharide for example has been observed in previous studies (27,44) and might make conditions more favorable for persistent carriage of pneumococci bearing the 6B capsule. In carriage studies, including the data presented here, serotype 6B pneumococci are more frequently isolated than many other serotypes (6,24).…”

Priming of Immunological Memory by Pneumococcal Conjugate Vaccine in Children Unresponsive to 23-Valent Polysaccharide Pneumococcal Vaccine

“…Thus, in (1,44). In addition, we and others have shown that PCVvaccination can overcome the impaired immune response to the plain pneumococcal polysaccharide in certain risk groups (22,30,32,39,41,46,55). However, antibody concentrations are not the only correlate of a protective immunity.…”

“…Here, we investigated the immunogenicity of PCV with a focus on its ability to induce an anamnestic response in patients with recurrent infections and an inability to respond to PPV immunization sufficiently (55). This so-called polysaccharide-specific immunodeficiency (PSI) is defined as an impaired immune response to polysaccharide antigens, while antibody response to protein antigens is intact.…”

Antibiotic Susceptibility in Relation to Penicillin-Binding Protein Genes and Serotype Distribution of Streptococcus pneumoniae Strains Responsible for Meningitis in Japan, 1999 to 2002

“…Meanwhile, various pneumococcal vaccines have been developed, ranging from a 23-polyvalent polysaccharide vaccine to conjugate vaccines, including 7-, 9-, or 11-polyvalency (7,16,47). Although all 90 recognized serotypes of S. pneumoniae appear to be pathogenic, how well a vaccine can cover serotypes representing invasive isolates is a key point.…”