The successful introduction of a conjugate vaccine for Haemophilus influenza in the childhood immunization program has spurred the development of a similar vaccine for Streptococcus pneumoniae. Several clinical trials are in progress which test the efficacy of polysaccharide-protein conjugates including serotypes 4, 9V, 6A, 6B, 14, 18C, 19F, and 23F. The efficacy is controlled by measuring antibody titers, immunoglobulin isotype distribution, avidity, and opsonophagocytosis. The ultimate goal is to correlate these parameters with protection.
In a recent paper Yu et al. (6) describe the presence of immunogenic noncapsular contaminants in the naturally derived pneumococcal capsular polysaccharides (PS) which interfere with general applied enzyme-linked immunosorbent assays (ELISAs). The ELISAs applied also use naturally derived polysaccharides as coat. Therefore, the ELISA for antibodies to pneumococcal capsules may not be serotype specific for some serum samples. The authors suggest improving the already highly standardized ELISA by absorbing the serum samples with unrelated capsular PS in addition to common cell wall polysaccharides. However, the search for unrelated, non-cross-reactive capsular PS as a preabsorbent to reduce incomplete serotype specificity in ELISA might be hampered by this aspecificity itself.
Although the chemical synthesis of oligosaccharides is traditionally rather difficult and time-consuming, in the past oligosaccharides for serotypes 17F, 23F, and 6B have been prepared and tested for their immunogenicity in mice and rabbits (2, 3). The synthesis and immunological testing of a set of overlapping oligosaccharides for types 6A, 3, and 14 are in progress (4, 5). So far, the data gathered on the immunogenicity of oligosaccharide conjugates indicate a high specificity of the response and a correlation of immunological parameters with protection (1). Along with the immunogenicity of these oligosaccharides, their applicability should be investigated for the improvement of the pneumococcal ELISA, in order to circumvent unwanted cross-reactivities which might obscure correlates of protection.
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