The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Piet A. Van Rijn - One of the best experts on this subject based on the ideXlab platform.
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application of bluetongue disabled infectious single animal disa vaccine for different Serotypes by vp2 exchange or incorporation of chimeric vp2
Vaccine, 2015Co-Authors: Femke Feenstra, Piet A. Van Rijn, Janny S PapAbstract:Bluetongue is a disease of ruminants caused by the bluetongue virus (BTV). Bluetongue outbreaks can be controlled by vaccination, however, currently available vaccines have several drawbacks. Further, there are at least 26 BTV Serotypes, with low cross protection. A next-generation vaccine based on live-attenuated BTV without expression of non-structural proteins NS3/NS3a, named Disabled Infectious Single Animal (DISA) vaccine, was recently developed for Serotype 8 by exchange of the Serotype determining outer capsid protein VP2. DISA vaccines are replicating vaccines but do not cause detectable viremia, and induce Serotype specific protection. Here, we exchanged VP2 of laboratory strain BTV1 for VP2 of European Serotypes 2, 4, 8 and 9 using reverse genetics, without observing large effects on virus growth. Exchange of VP2 from Serotype 16 and 25 was however not possible. Therefore, chimeric VP2 proteins of BTV1 containing possible immunogenic regions of these Serotypes were studied. BTV1, expressing 1/16 chimeric VP2 proteins was functional in virus replication in vitro and contained neutralizing epitopes of both Serotype 1 and 16. For Serotype 25 this approach failed. We combined VP2 exchange with the NS3/NS3a negative phenotype in BTV1 as previously described for Serotype 8 DISA vaccine. DISA vaccine with 1/16 chimeric VP2 containing amino acid region 249-398 of Serotype 16 raised antibodies in sheep neutralizing both BTV1 and BTV16. This suggests that DISA vaccine could be protective for both parental Serotypes present in chimeric VP2. We here demonstrate the application of the BT DISA vaccine platform for several Serotypes and further extend the application for Serotypes that are unsuccessful in single VP2 exchange.
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Bluetongue Viruses Based on Modified-Live Vaccine Serotype 6 with Exchanged Outer Shell Proteins Confer Full Protection in Sheep against Virulent BTV8
2012Co-Authors: Mieke Maris-veldhuis, Piet A. Van RijnAbstract:Since 1998, Bluetongue virus (BTV)-Serotypes 1, 2, 4, 9, and 16 have invaded European countries around the Mediterranean Basin. In 2006, a huge BT outbreak started after incursion of BTV Serotype 8 (BTV8) in North-Western Europe. IN 2008, BTV6 and BTV11 were reported in the Netherlands and Germany, and in Belgium, respectively. In addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which was recognized as a new Serotype of BTV (BTV25). The (re-)emergency of BTV Serotypes needs a rapid response to supply effective vaccines. Reverse genetics has been developed for BTV1 and more recently also for BTV6. This latter strain, BTV6/net08, is closely related to live-attenuated vaccine for Serotype 6 as determined by full genome sequencing. Here, we used this strain as backbone and exchanged segment 2 and 6, respectively Seg-2 (VP2) and Seg-6 (VP5), for those of BTV Serotype 1 and 8 using reverse genetics. These so-called ‘Serotyped ’ vaccine viruses, as mono-Serotype and multi-Serotype vaccine, were compared for their protective capacity in sheep. In general, all vaccinated animals developed a neutralizing antibody response against their respective Serotype. After challenge at three weeks post vaccination with cell-passaged, virulent BTV8/net07 (BTV8/net07/e1/bhkp3) the vaccinated animals showed nearly no clinical reaction. Even more, challenge virus could not be detected, and seroconversion or boostering after challenge was negligible. These data demonstrate that all sheep were protected from a challenge with BTV8/net07, since sheep of the control group showed viremia, seroconversion and clinical signs that are specific fo
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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sequential multiplex pcr approach for determining capsular Serotypes of streptococcus pneumoniae isolates
Journal of Clinical Microbiology, 2006Co-Authors: Rekha Pai, Robert E Gertz, Bernard BeallAbstract:Accurate serotyping is essential to monitor the changes in the seroepidemiology of Streptococcus pneumoniae. We devised a simple and schematic sequence-based system of seven multiplex PCRs, in a sequence order based upon Active Bacterial Core surveillance (ABCs) Serotype distribution during 2002 to 2003, to reliably deduce specific pneumococcal Serotypes. A total of 421 isolates from ABCs were randomly chosen to evaluate this system. Two hundred twenty-nine of the isolates (54.3%) were specifically assigned 1 of 17 Serotypes by the multiplex PCR system, with the results in complete concordance with conventional serotyping. One hundred seventy-two additional isolates (40.9%) were assigned to 11 specific sets of 2 to 4 Serotypes that with one exception (Serotypes 6A and 6B) consisted of the single frequently occurring targeted Serotype and 1 to 3 additional rare Serotypes primarily within the same serogroup as the targeted Serotype. Only 20 isolates (4.8%) could not be assigned specific Serotypes or Serotype sets, since they were either of rare Serotypes not included in the assay design or were nonSerotypeable. Overall, we found this system to be highly reliable, with the potential to greatly reduce our reliance upon conventional serotyping. Especially important is the capability of this system to give Serotype-determining potential to any facility that lacks the expensive typing sera and expertise needed for conventional serotyping yet has the modest equipment necessary for DNA amplification and electrophoresis.
Nicholas G Reich - One of the best experts on this subject based on the ideXlab platform.
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interactions between Serotypes of dengue highlight epidemiological impact of cross immunity
Journal of the Royal Society Interface, 2013Co-Authors: Nicholas G Reich, Sourya Shrestha, Aaron A King, Pejman Rohani, Justin Lessler, Siripen Kalayanarooj, Inkyu YoonAbstract:Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue Serotypes induces protective immunity to that Serotype, but does not confer long-term protection against infection by other Serotypes. The immunological interactions between Serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 Serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between Serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other Serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.
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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pneumococcal polysaccharide vaccine at 12 months of age produces functional immune responses
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Paul V Licciardi, Moon H Nahm, Anne Balloch, Fiona M Russell, Robert L Burton, Jisheng Lin, E K Mulholland, Mimi L K TangAbstract:Background Infections with Streptococcus pneumoniae (pneumococcus) are a cause of significant child mortality. Pneumococcal glycoconjugate vaccines are expensive and provide limited Serotype coverage. The 23-valent pneumococcal polysaccharide vaccine (Pneumovax) might provide wider Serotype coverage but is reported to be weakly immunogenic in children less than 2 years of age. We have previously reported that Pneumovax administered to healthy 12-month-old Fijian infants elicits significant Serotype-specific IgG responses. However, the functional capacity of these responses in 12-month-old infants is not known. Objective We sought to assess the functional, Serotype-specific immune response of 12-month-old infants after immunization with Pneumovax. Methods Functional responses of 12-month-old infants were assessed by using the opsonophagocytic and antibody avidity assay against 8 Serotypes and 23 Serotypes, respectively. Results Seventy-one percent of infants produced strong opsonophagocytic activity against 4 of 8 Serotypes, and 30% produced high-avidity Serotype-specific IgG antibodies to 10 of 23 Serotypes at 2 weeks after Pneumovax. Responses were protective for most Serotypes that cause disease in Western countries, whereas responses to most of the epidemiologically relevant Serotypes for developing countries were low. Conclusion This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month-old infants. Pneumovax induced functional antibody responses to several Serotypes causing disease in Western countries but induced poorer responses to Serotypes that are responsible for the majority of disease in developing countries. Pneumovax might be of benefit in some populations, but further studies are required before this can be recommended in developing countries.
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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.
