Functional Antibodies Elicited by Two Heptavalent Pneumococcal Conjugate Vaccines in the Finnish Otitis Media Vaccine Trial

Ekström, Nina; Väkeväinen, Merja; Verho, Jouko; Kilpi, Terhi; Käyhty, Helena

doi:10.1128/iai.01673-06

Cited by 41 publications

(31 citation statements)

References 44 publications

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“…Previous studies have suggested that antibodies against serotype 19F have lower functionality than antibodies against the other serotypes included in 7vCRM (9,11,14,37). Despite this apparently weaker protection against serotype 19F, invasive pneumococcal disease due to serotype 19F is well controlled by vaccination with 7vCRM.…”

Section: Discussionmentioning

confidence: 99%

Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines

Poolman

Frasch

Nurkka

et al. 2011

Clin Vaccine Immunol

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We found that conjugation of the serotype 19F polysaccharide using reductive amination (as in 7vCRM) resulted in the formation of at least one additional epitope that is not present in the native form of the 19F polysaccharide or following 19F conjugation using a bifunctional spacer (as in the prototype vaccine 7vOMPC) or cyanylation (as in PHiD-CV). We also found that pneumococcal vaccines conjugated using cyanylation induce more opsonophagocytic antibodies against serotype 19F and a considerably higher level of cross-opsonophagocytic antibodies against serotype 19A than vaccines conjugated using reductive amination. In conclusion, these results suggest that the conjugation method can influence the functionality of the antibodies induced against the homologous serotype 19F and the cross-reactive serotype 19A of S. pneumoniae. 7vCRM (Prevenar/Prevnar; Pfizer, Inc.) contains capsular polysaccharides of Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, each conjugated to the nontoxic cross-reacting mutant diphtheria toxin CRM 197 . Serotype 19A was not included in 7vCRM, because it was expected that the immunological similarities with vaccine serotype 19F would elicit sufficient cross-protection, as observed for serotype 6B and the related serotype 6A (26,38,48,52). Serotypes 19F and 19A are indeed closely related biochemically (38, 52). Serotype 19A and 19F polysaccharides are composed of similar trisaccharide units polymerized through phosphate diester groups and differ only in the position of the linkage to the ␣-L-rhamnose residue: ␣(132) for 19F and ␣(133) for 19A (19,29

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Section: Discussionmentioning

confidence: 99%

Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines

Poolman

Frasch

Nurkka

et al. 2011

Clin Vaccine Immunol

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“…Despite moderate resistance to complement deposition, a very high concentration of serotype-specific antibodies was found here and previously (33) to be required for opsonophagocytosis of serotype 19F strains, suggesting inferior functional properties of antibodies. The data from clinical trials demonstrate a correlation of serotype-specific vaccine efficacy with opsonophagocytic activity of the antibodies (14,46). The antibody concentration required for 50% opsonophagocytic killing depends on the capsular serotype and up to five times higher antibody concentrations have been reported to be required for killing serotype 19F compared to 6B (14,33,43,46,59).…”

Section: Vol 78 2010mentioning

confidence: 96%

Serotype-Related Variation in Susceptibility to Complement Deposition and Opsonophagocytosis among Clinical Isolates of Streptococcus pneumoniae

et al. 2010

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The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae; it affects complement resistance and shields the bacterium from phagocytes. Certain capsular serotypes appear to be better able to cause invasive disease than others. Serotypes 1 and 5 are common causes of invasive disease but are rarely isolated from healthy carriers, whereas serotypes 6B and 23F are more frequently isolated from carriage than invasive disease. We have recently shown that serotypes 6B and 19F differ in resistance to complement C3 deposition and opsonophagocytic killing. In this study we assessed the complement resistance and susceptibility to opsonophagocytosis of several other serotypes targeted by the pneumococcal conjugate vaccines. Clinical isolates of serotypes 1, 4, 5, 14, 18C, and 23F were tested along reference strains of corresponding capsular types. The concentration of anticapsular antibodies required for opsonophagocytic killing correlated inversely with C3 deposition on the serotype. Serotype 1 was the most resistant of the clinical isolates to C3 deposition and, along with serotypes 5 and 19F, required the highest concentration of capsule antibodies for opsonophagocytic killing, whereas serotype 23F was the most sensitive to opsonophagocytosis. Sensitivity to C3 deposition and opsonophagocytosis was associated with serotype-specific mortality of invasive pneumococcal disease, suggesting that the primary pathogens, such as serotypes 1 and 5, are more resistant to complement and require a higher concentration of capsule antibodies for opsonophagocytic killing than the opportunistic serotypes such as 6B and 23F, which are associated with a more severe disease outcome.

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“…This protocol was initially developed for evaluation of the immunogenicities of pneumococcal vaccines. On the basis of a meta-analysis of the results of the various vaccine trials (3,8,12,15,19), WHO recommends the use of an antibody concentration of 0.35 g/ml as a correlate of protection if it is assessed by ELISA (29). This recommended protective concentration is identical for all serotypes.…”

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confidence: 99%

Optimization and Application of a Multiplex Bead-Based Assay To Quantify Serotype-Specific IgG againstStreptococcus pneumoniaePolysaccharides: Response to the Booster Vaccine after Immunization with the Pneumococcal 7-Valent Conjugate Vaccine

Elberse

Tcherniaeva

Berbers

et al. 2010

Clin Vaccine Immunol

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We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre-and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R 2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R 2 was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 g/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.

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Functional Antibodies Elicited by Two Heptavalent Pneumococcal Conjugate Vaccines in the Finnish Otitis Media Vaccine Trial

Cited by 41 publications

References 44 publications

Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines

Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines

Serotype-Related Variation in Susceptibility to Complement Deposition and Opsonophagocytosis among Clinical Isolates of Streptococcus pneumoniae

Optimization and Application of a Multiplex Bead-Based Assay To Quantify Serotype-Specific IgG againstStreptococcus pneumoniaePolysaccharides: Response to the Booster Vaccine after Immunization with the Pneumococcal 7-Valent Conjugate Vaccine

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