Using two monoclonal antibodies, we found subtypes among pneumococcal isolates that are typed as serotype 6A by the quellung reaction. The prevalent subtype bound to both monoclonal antibodies and was labeled here 6A␣, whereas the minor subtype bound to only one monoclonal antibody and was labeled 6A. To determine the biochemical nature of the two serologically defined subtypes, we purified capsular polysaccharides (PSs) from the two subtypes and examined their chemical structures with gas-liquid chromatography and mass spectrometry. The study results for 6A␣ PS are consistent with the previously published structure of 6A PS, which is 32) galactose (133) glucose (133) rhamnose (133) Streptococcus pneumoniae is a major human pathogen that is responsible for a large percentage of cases of pneumonia, meningitis, otitis media, and sepsis (6). All pathogenic pneumococci are known to display one of many structurally diverse carbohydrate capsules, which shield pneumococci from host phagocytes and increase their pathogenicity (2). Antisera to a capsule type can be used to treat patients infected with the pneumococci expressing that capsule type (4). Consequently, for the past century, the serological types of pneumococcal capsules have been extensively investigated with quellung reactions. These studies have culminated in identifying 90 different pneumococcal capsules with distinct serological patterns (9) and chemical structures (10).Not all 90 serotypes are equally pathogenic. For instance, serotypes 6A and 6B account for 4.7% and 7%, respectively, of cases of invasive pneumococcal disease in the U.S. population (19,20). Because of their medical importance, the molecular natures of serotype 6A and its related serotype, serotype 6B, have been studied extensively. Biochemical studies found that the capsular polysaccharides (PSs) of serotypes 6A and 6B are linear polymers with a repeating unit containing four monosaccharides/alditols: rhamnose, ribitol-phosphate (P), galactose, and glucose (10). The two PSs are identical except for a difference in the linkage between rhamnose and ribitol (see Fig. 6).Currently available pneumococcal vaccines are designed to elicit antibodies to the capsular PSs of the most common pneumococcal serotypes. Since vaccine-induced immunoprotection is serotype specific, serotyping pneumococcal isolates from patients is an important tool for monitoring the effectiveness of pneumococcal vaccines (3). Because the classical quellung reaction with rabbit antisera is tedious to perform (13), we have developed a new serotyping system based on mouse monoclonal antibodies (mAbs) and a multiplexed immunoassay (27). While validating the new system, we found that a minor fraction of the isolates determined to be serotype 6A by quellung reaction bound to one 6A-specific mAb (Hyp6AG1) but not to the other (Hyp6AM3), whereas the majority of the serotype 6A isolates bound to both mAbs (12). To distinguish between the isolates, we have labeled the isolates reacting with both mAbs as 6A␣ and those reacting wit...
These data indicate that 10 countries of the Region continue to have high quality laboratory-based surveillance for pneumococcal disease thus generating valuable information so that healthcare decision makers may prioritize interventions. The heptavalent vaccine will potentially cover from 52.4% to 76.5% of strains causing invasive pneumococcal disease and the 13 valent from 76.7% to 88.3%.
In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12-23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio×100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8-21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8-11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7-99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.
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