18 research outputs found

    Functionally Inert HIV-Specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and Children

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    The highly sensitive quantitation of virus-specific CD8+ T cells using major histocompatibility complex–peptide tetramer assays has revealed higher levels of cytotoxic T lymphocytes (CTLs) in acute and chronic virus infections than were recognized previously. However, studies in lymphocytic choriomeningitis virus infection have shown that tetramer assays may include measurement of a substantial number of tetramer-binding cells that are functionally inert. Such phenotypically silent CTLs, which lack cytolytic function and do not produce interferon (IFN)-γ, have been hypothesized to explain the persistence of virus in the face of a quantitatively large immune response, particularly when CD4 help is impaired. In this study, we examined the role of functionally inert CTLs in chronic HIV infection. Subjects studied included children and adults (n = 42) whose viral loads ranged from <50 to >100,000 RNA copies/ml plasma. Tetramer assays were compared with three functional assays: enzyme-linked immunospot (Elispot), intracellular cytokine staining, and precursor frequency (limiting dilution assay [LDA]) cytotoxicity assays. Strong positive associations were observed between cell numbers derived by the Elispot and the tetramer assay (r = 0.90). An even stronger association between tetramer-derived numbers and intracellular cytokine staining for IFN-γ was present (r = 0.97). The majority (median 76%) of tetramer-binding cells were consistently detectable via intracellular IFN-γ cytokine staining. Furthermore, modifications to the LDA, using a low input cell number into each well, enabled LDAs to reach equivalence with the other methods of CTL enumeration. These data together show that functionally inert CTLs do not play a significant role in chronic pediatric or adult HIV infection

    Software and reference sequence for inferring serotype from Illumina sequence data

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    This software is a simple script that uses BWA mapping to identify the likely serogroup of a pneumococcal isolate based on paired end FASTQ data

    Predicted protein coding sequences from 616 S. pneumoniae isolates

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    This compressed archive comprises a FASTA file containing the DNA sequences of all predicted protein coding sequences from 616 S. pneumoniae isolates collected from Massachusetts between 2001 and 2007. Each sequence is labelled with a unique identifier (of the form, “ERSX_Y”, where “ERSX” is the sample accession code in the European Nucleotide Archive and Y is an incrementing index) and, where applicable, the COG of the translated protein (of the form, “SPARC1_CLSZ” or “SPARC1_CLSTZ”, where Z is a number)

    Data from: Population genomic datasets describing the post-vaccine evolutionary epidemiology of Streptococcus pneumoniae

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    Streptococcus pneumoniae is common nasopharyngeal commensal bacterium and important human pathogen. Vaccines against a subset of pneumococcal antigenic diversity have reduced rates of disease, without changing the frequency of asymptomatic carriage, through altering the bacterial population structure. These changes can be studied in detail through using genome sequencing to characterise systematically-sampled collections of carried S. pneumoniae. This dataset consists of 616 annotated draft genomes of isolates collected from children during routine visits to primary care physicians in Massachusetts between 2001, shortly after the seven valent polysaccharide conjugate vaccine was introduced, and 2007. Also made available are a core genome alignment and phylogeny describing the overall population structure, clusters of orthologous protein sequences, software for inferring serotype from Illumina reads, and whole genome alignments for the analysis of closely-related sets of pneumococci. These data can be used to study both bacterial evolution and the epidemiology of a pathogen population under selection from vaccine-induced immunity

    Predicted protein sequences from 616 S. pneumoniae isolates

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    This compressed archive comprises a FASTA file containing the amino acid sequences translated from all predicted protein coding sequences from 616 S. pneumoniae isolates collected from Massachusetts between 2001 and 2007. Each sequence is labelled with a unique identifier (of the form, “ERSX_Y”, where “ERSX” is the sample accession code in the European Nucleotide Archive and Y is an incrementing index) and, where applicable, the COG to which the protein belongs (of the form, “SPARC1_CLSZ” or “SPARC1_CLSTZ”, where Z is a number)

    Maximum likelihood phylogeny based on the core genome alignment of 616 Streptococcus pneumoniae isolates

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    Newick format maximum likelihood phylogeny generated using the 106,196 polymorphic sites in a core genome alignment of 616 Streptococcus pneumoniae isolates. The tree was produced by RAxML using the general time reversible substitution model with a four category gamma distribution to correct for rate heterogeneity

    Draft reference genome sequences for each of the 15 sequence clusters

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    This compressed archive contains 15 FASTA draft de novo assemblies used to generate the whole genome alignments within each sequence cluster. The files are named according to the sequence cluster and taxon identifier of the isolate to which the contigs relate

    Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

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    Abstract Background Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort.</p
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