Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates. They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans. However, little is known of the natural development of antibodies to these proteins in humans. The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children. Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers. All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.

Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05).

Antibody-mediated killing of Streptococcus pneumoniae (pneumococcus) by phagocytes is an important mechanism of protection of the human host against pneumococcal infections. Measurement of opsonophagocytic antibodies by use of a standardized opsonophagocytic assay (OPA) is important for the evaluation of candidate vaccines and required for the licensure of new pneumococcal conjugate vaccine formulations. We assessed agreement among six laboratories that used their own optimized OPAs on a panel of 16 human reference sera for 13 pneumococcal serotypes. Consensus titers, estimated using an analysis-of-variance (ANOVA) mixed-effects model, provided a common reference for assessing agreement among these laboratories. Agreement was evaluated in terms of assay accuracy, reproducibility, repeatability, precision, and bias. We also reviewed four acceptance criterion intervals for assessing the comparability of protocols when assaying the same reference sera. The precision, accuracy, and concordance results among laboratories and the consensus titers revealed acceptable agreement. The results of this study indicate that the bioassays evaluated in this study are robust, and the resultant OPA values are reproducible for the determination of functional antibody titers specific to 13 pneumococcal serotypes when performed by laboratories using highly standardized but not identical assays. The statistical methodologies employed in this study may serve as a template for evaluating future multilaboratory studies.

We have investigated the association between the concentration of anti-polysaccharide pneumococcal capsule-specific (anti-PS) immunoglobulin G and the killing activity, in serum, in invasive pneumococcal disease (IPD) events and response to 23-valent polysaccharide vaccine in human immunodeficiency virus (HIV)-infected Ugandans. Case patients with IPD had lower concentrations of anti-PS IgG before and after vaccination and before the IPD event ( for 5 [i.e., 4, 9V, P ! .01 14, 18C, and 19F] of 6 serotypes assessed). After vaccination, case patients were less likely than were control subjects to develop detectable serum killing activity against the 2 serotypes tested-for 19F, this activity was detected in 16% of case patients versus 37% of control subjects ( ); for 23F, it was P p .08 detected in 11% of case patients versus 40% of control subjects ( ). Thus, absolute concentration of anti-PS IgG and P p .02 an attenuated response to polysaccharide are associated with risk of IPD in HIV-infected adults.Streptococcus pneumoniae is a frequent and serious infection in HIV-1-infected adults in Africa [1]. When control of invasive pneumococcal disease (IPD) by 23-valent pneumococcal poly-

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The presence of Streptococcus pneumoniae in the upper respiratory tract was studied in 318 Filipino children less than 5 years old with an acute lower respiratory tract infection. Nasopharyngeal samples were obtained from 292 children. With both quantitative bacterial culture and detection of capsular polysaccharide antigens by coagglutination, counterimmunoelectrophoresis, and latex agglutination, pneumococci were found in 160 (70%) of the 227 samples eligible for analysis. Culture was positive in 115 samples and antigen was positive in 140 samples. The culture isolation rate was significantly lower if the patient had received antimicrobial agents in the 48 h prior to the sampling. The seven most common types or groups of pneumococci were 6, 14, 19, 23, 15, 7, and 11, which together accounted for 64% of all pneumococcal findings.