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Moon H Nahm - One of the best experts on this subject based on the ideXlab platform.
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ficolin 2 binds to serotype 35b pneumococcus as it does to Serotypes 11a and 31 and these Serotypes cause more infections in older adults than in children
PLOS ONE, 2018Co-Authors: Aaron K Geno, Brady L Spencer, Sejong Bae, Moon H NahmAbstract:Among 98 Serotypes of Streptococcus pneumoniae, only a small subset regularly causes invasive pneumococcal diseases (IPD). We previously demonstrated that serotype 11A binds to ficolin-2 and has low invasiveness in children. Epidemiologic data suggested, however, that serotype 11A IPD afflicts older adults, possibly indicating reduced ficolin-2-mediated immune protection. Therefore, we studied the epidemiology of ficolin-2-bound Serotypes. We obtained IPD case data from the United States Centers for Disease Control and Prevention. We studied three prominent ficolin-2-bound Serotypes and their acetyltransferase-deficient variants for ficolin-2 binding and ficolin-2-mediated complement deposition with flow-cytometry. We determined the age distributions of these Serotypes from the obtained epidemiologic data. We discovered that the serotype 35B capsule is a novel ficolin-2 ligand due to O-acetylation via WciG. Ficolin-2-mediated complement deposition was observed on Serotypes 11A and 35B but not serotype 31 or any O-acetyl transferase deficient derivatives of these Serotypes. Serotypes 11A, 35B, and 31 cause more IPD among older adults than children. Studies of the three Serotypes provide additional evidence for ficolin-2 providing innate immunity against IPD. The skewed age distribution of the three Serotypes suggests that older adults have reduced ficolin-2-mediated immunity and are more susceptible to these Serotypes.
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spectrum of pneumococcal serotype 11a variants results from incomplete loss of capsule o acetylation
Journal of Clinical Microbiology, 2014Co-Authors: Juan J Calix, Allison M Brady, Jamil S Saad, Moon H NahmAbstract:Streptococcus pneumoniae is a significant bacterial pathogen that expresses >90 capsule Serotypes. Conventional serotyping methods assume that each serotype is a genetically and antigenically distinct entity; however, recent investigations have revealed pneumococcal isolates that cannot be unambiguously serotyped because they share the properties of more than one serotype. Here, we employed a novel serotyping method and NMR spectroscopy to examine clinical isolates sharing properties of Serotypes 11A and 11E. These ambiguous clinical isolates were provisionally named 11A variant (11Av) isolates. Serotype 11A pneumococci characteristically express capsule β-galactose-6-O-acetylation (βGal6OAc) mediated by the capsule synthesis gene wcjE, while 11E strains contain loss-of-function mutations in wcjE and completely lack the expression of βGal6OAc. Although 11Av isolates also contained mutated wcjE alleles, 11Av clinical isolates were composed of antigenically homogeneous bacteria expressing reduced amounts of 11A-specific capsule antigen. NMR data confirmed reduced but detectable amounts of βGal6OAc on 11Av capsule polysaccharide. Furthermore, the transformation of strains with wcjE alleles from 11Av strains was sufficient to restore partial βGal6OAc in an 11E background. We conclude that, instead of being distinct entities, Serotypes 11A and 11E represent two extremes of an antigenic spectrum resulting from variable capsule O-acetylation secondary to heterologous wcjE mutations. These findings challenge whether all clinically relevant pneumococci can be definitively categorized into distinct Serotypes.
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the 13 valent pneumococcal conjugate vaccine pcv13 elicits cross functional opsonophagocytic killing responses in humans to streptococcus pneumoniae Serotypes 6c and 7a
Vaccine, 2011Co-Authors: David A Cooper, Moon H Nahm, Mohinder Sidhu, Philip Fernsten, Kathrin U JansenAbstract:The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven Serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 Serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to Serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these Serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related Serotypes not directly covered by the vaccine.
U Vecht - One of the best experts on this subject based on the ideXlab platform.
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distribution of capsular types and production of muramidase released protein mrp and extracellular factor ef of streptococcus suis strains isolated from diseased pigs in seven european countries
Veterinary Microbiology, 2000Co-Authors: Henk J Wisselink, Hilde E Smith, Norbert Stockhofezurwieden, Klaas Peperkamp, U VechtAbstract:Streptococcus suis strains (n=411), isolated from diseased pigs in seven European countries were serotyped using specific antisera against serotype 1 to 28, and were phenotyped on the basis of their muramidase-released-protein (MRP) and extracellular-factor protein (EF) production. Overall, S. suis serotype 2 appeared to be most prevalent (32%), followed by serotype 9 (20%) and serotype 1 (12%). Serotype 2 was most frequently isolated in France, Italy and Spain, whereas serotype 9 was most frequently isolated in Belgium, The Netherlands and Germany. In the United Kingdom Serotypes 1 and 14 were most frequently isolated. High percentages of S. suis serotype 1, 2, 1/2 and 14 strains, isolated from tissues associated with S. suis infections such as brain, serosa, joint, heart and organs expressed the EF-protein, indicating that in these Serotypes expression of EF is likely to be associated with virulence. In contrast, strains belonging to serotype 7 and 9, isolated from tissues associated with S. suis infections did not produce EF. These results strongly suggest that in the Serotypes 7 and 9 EF expression is not related to virulence. More than 80% of the S. suis serotype 9 strains produced an MRP* protein, a high molecular variant of the 136kDa MRP. Expression of MRP* in serotype 9 strains is possibly associated with virulence.
Elizabeth Miller - One of the best experts on this subject based on the ideXlab platform.
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pneumococcal carriage in children and their household contacts six years after introduction of the 13 valent pneumococcal conjugate vaccine in england
PLOS ONE, 2018Co-Authors: Jo Southern, Nick Andrews, Pauline Waight, Pamela Sandu, Carmen L Sheppard, Norman K Fry, Albert Jan Van Hoek, Elizabeth MillerAbstract:Background In April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase. Methods and findings Families with a child aged twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the Serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the Serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 Serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 Serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013. Conclusions There was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to Serotypes 3 and 19A may not be achieved by PCV13.
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pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in england
Vaccine, 2014Co-Authors: Albert Jan Van Hoek, Shamez N Ladhani, Mary P E Slack, Nick Andrews, Pauline Waight, Carmen L Sheppard, Timothy G Harrison, Elizabeth MillerAbstract:Background/Aims In April 2010 the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent PCV. We investigated pneumococcal carriage in children eligible for PCV7 or PCV13 and their household contacts. Methods Eligible families in Hertfordshire and Gloucester were identified and a nasopharyngeal swab obtained from consenting household members between July 2012 and March 2013. Samples were cultured for Streptococcus pneumoniae and serotyped by standard methods. For each serotype the ratio of its prevalence in invasive pneumococcal disease (IPD) to its carriage prevalence (case:carrier ratio, CCR) was calculated. Results were compared with previous carriage studies in 2001/2002 and 2008/2009, before and after PCV7 introduction. Results 217 households were included. Among <5-year olds 47.7% (95% confidence interval 41.8–53.5) were carrying a pneumococcus compared with 51.0% (95% CI: 44.0–58.0) in 2008/2009 and 48.4% (95% CI: 44.1–52.7) in 2001/2002. The odds of carrying a PCV7 serotype was significantly reduced in 2008/2009 (0.07, 95% CI: 0.03–0.16) and 2012/2013 (0.01 95% CI: 0.00–0.07) relative to 2001/2002, while the odds of carrying any of the extra six PCV13 Serotypes increased after PCV7 introduction (1.38, 95%CI: 0.73–2.59) but declined significantly after PCV13 introduction (0.05, 95%CI: 0.01–0.37). The CCRs for the frequently carried Serotypes were relatively low, with the highest CCR observed for Serotypes 7F, 19A, 3, 8, and 33F. Across the three carriage studies, CCR estimates were stable for nearly all Serotypes. Conclusion Carriage of additional PCV13 Serotypes has rapidly reduced post-PCV13 introduction in both vaccinated and unvaccinated individuals with a continued decline in transmission of PCV7 Serotypes. Carriage rates in children remain unchanged, but the low CCRs of replacing Serotypes would be expected to further reduce overall IPD across all age groups.
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changes in molecular epidemiology of streptococcus pneumoniae causing meningitis following introduction of pneumococcal conjugate vaccination in england and wales
Journal of Clinical Microbiology, 2013Co-Authors: Bruno Pichon, Shamez N Ladhani, Mary P E Slack, Anne Segondspichon, Nick Andrews, Pauline Waight, Elizabeth Miller, Rob GeorgeAbstract:The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two Serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson's diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 Serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual Serotypes. Replacement disease following PCV7 introduction was mainly due to Serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 Serotypes, including some not covered by the 13-valent vaccine, such as Serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance.
Bernard Beall - One of the best experts on this subject based on the ideXlab platform.
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geographic variation in invasive pneumococcal disease following pneumococcal conjugate vaccine introduction in the united states
Clinical Infectious Diseases, 2011Co-Authors: Jennifer Rosen, Ann Thomas, Catherine Lexau, Art Reingold, James L Hadler, Lee H Harrison, Nancy M Bennett, William Schaffner, Monica M Farley, Bernard BeallAbstract:Background. Rates of invasive pneumococcal disease (IPD) varied among the United States before pneumococcal conjugate vaccine (PCV7) introduction. We compared trends in IPD rates among diverse US sites over 10 years since PCV7 introduction. Methods. Patients with IPD of all ages were identified through active population and laboratory-based surveillance in 8 geographic areas under continuous surveillance during 1998‐2009. Isolates were serotyped. IPD incidence rates and percent changes were calculated by site, serotype group, age, and year. Results. Reductions in rates of IPD ranged, by site, from 19 to 29.9 cases per 100,000 population during 1998‐ 1999 to 11.2‐18.0 cases per 100,000 population during 2009 (rate reduction, 5.1‐15.3 cases per 100,000 population). Reductions in IPD rates among children aged ,5 years ranged from 35.7 to 117.2 cases per 100,000 population across the sites. Reductions in rates of IPD due to PCV7 Serotypes were seen in all age groups at all sites, ranging from 12 to 21.4 cases per 100,000 population during 1998‐1999 to ,2 cases per 100,000 population during 2009 (92%‐98% reductions). Serotype 19A rates ranged from 0.4 to 1.5 cases per 100,000 population during 1998‐1999 to 1.3 to 3.4 cases per 100,000 population during 2009 (rate difference, 0.9‐2.8 cases per 100,000 population); modest increases were observed for most age groups across the sites. Rates of IPD due to all other Serotypes ranged from 6.3 to 10.3 cases per 100,000 population during 1998‐1999 to 8.3‐13.6 cases per 100,000 population during 2009 (rate difference, 20.4 to 5.7 cases per 100,000 population). Across the sites, the greatest rate increases were seen in the 50‐64 and .65 year age groups. Conclusions. Reductions in IPD due to vaccine Serotypes were consistent across sites. Changes in serotype 19A and all other Serotypes were variable. Although relative increases in non‐vaccine type Serotypes were large in some sites, absolute rate increases were small.
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Serotype-specific typing antisera for pneumococcal serogroup 6 Serotypes 6A, 6B, and 6C.
Journal of clinical microbiology, 2010Co-Authors: Nikkol Melnick, Terry A. Thompson, Bernard BeallAbstract:Streptococcus pneumoniae strains can express one of at least 92 capsular Serotypes. To our knowledge, our laboratory is one of two that maintain antisera for resolution of the first 90 discovered pneumococcal Serotypes (4; unpublished data). Recently, the evaluation of serogroup 6 isolates using monoclonal antibodies led to the discovery of the 91st serotype, 6C (7), which has become the prevalent invasive serogroup 6 serotype within the United States (2, 9). The pneumococcal 7-valent conjugate vaccine (PCV7) does not protect against it, and it is not included within the newly licensed 13-valent conjugate vaccine. In addition, serotype 6C carriage may also be common within PCV7-vaccinated populations (3). Prior to the discovery of serotype 6C, Serotypes 6A and 6B were the 2 known serogroup 6 Serotypes. CDC antisera for quellung-based resolution of Serotypes 6A and 6B are designated as Danish factors 6b and 6c (DF-6b and DF-6c), respectively. Our original DF-6b antiserum was positive for both 6A and 6C Serotypes, preventing their resolution (Table (Table11). TABLE 1. DF-6b, DF-6c, and DF-6d quellung results We produced DF-6d antiserum specific to serotype 6C and DF-6b antiserum specific to 6A as follows. New Zealand White female rabbits were inoculated with S. pneumoniae Serotypes 6C or 6A formalin-fixed whole cells. The inocula consisted of serotype 6C or 6A cell suspensions (108 to 109 cells per ml in phosphate-buffered saline), which were administered intravenously via the marginal ear vein (Table (Table2).2). Blood was drawn after week 4 of dosing, and serum was evaluated for antibody titer to serotype 6C or 6A and cross-reactivity to Serotypes 6A, 6B, and 6C by the quellung reaction. Cross-reactivity was removed from DF-6d by absorbing the serum with formalin-fixed cells of Serotypes 6A and 6B. DF-6b antiserum was absorbed with formalin-fixed cells of Serotypes 6B and 6C. The resulting DF-6d antiserum was specific for serotype 6C only, and DF-6b was specific to 6A only (Table (Table11). TABLE 2. Dosing schedule for preparation of antisera The specificity of DF-6b, DF-6c, and DF-6d antisera was evaluated with stock strains and 159 clinical isolates, each representing one of the Serotypes 6A, 6B, or 6C. For all strains, Neufeld quellung results were compared to PCR testing specific for the serotype 6C wicN6C locus (2, 7, 8) with no inconsistencies observed. We have replaced our previous methods with these procedures for producing specific factor sera against Serotypes 6A and 6C. We have now learned that Statens Serum Institute (SSI) has also recently produced factor 6d against serotype 6C (5). Our DF-6b, unlike the SSI factor 6b, is now serotype 6A specific and does not cross-react against serotype 6C. Serotype 6C-specific antiserum will be useful for laboratories which utilize quellung testing. Recently a fourth serogroup 6 serotype, serotype 6D, has been discovered in nature (1, 6) that is recognizable by a positive quellung test for serotype 6B combined with a positive PCR test for wciN6C. Despite extensive screening, we have not yet encountered this serotype (2). We do not yet know if our DF-6d antiserum would cross-react with serotype 6D. Consequently we screen all quellung test 6B strains by PCR for the presence of wciN6C (2, 8).
Mario Jacques - One of the best experts on this subject based on the ideXlab platform.
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Serotyping of Canadian isolates of Treponema hyodysenteriae and description of two new Serotypes.
Journal of clinical microbiology, 1991Co-Authors: M. Belanger, Mario JacquesAbstract:A total of 30 isolates of Treponema hyodysenteriae collected in the Saint-Hyacinthe (Quebec, Canada) area were serotyped by agar gel double immunodiffusion by using extracted lipopolysaccharide and hyperimmune rabbit antisera. Only 17% (5 of 30) of the isolates were typed with antisera specific for each of the seven known Serotypes of T. hyodysenteriae. Antisera raised against 11 untypeable local isolates were then produced and tested against each lipopolysaccharide extract. Results showed two serologically distinct groups among 21 of the 25 untypeable isolates. The isolates in each group shared identical antigens. No detectable reactions could be observed between antisera raised against these 11 isolates and the antigens extracted from 7 reference serotype strains. On the basis of these results, two new Serotypes of T. hyodysenteriae, Serotypes 8 and 9, are proposed. We also propose isolate FM 88-90 as the reference strain for serotype 8 and isolate FMV 89-3323 as the reference strain for serotype 9. These two new Serotypes, which represented 70% of the isolates tested, seem to be the major Serotypes found in the province of Quebec.
