13 research outputs found

    Genes downregulated in melioidosis and tuberculosis, arranged by pathway.

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    <p>IFN = interferon, IGF = insulin-like growth factor, IL = interleukin, NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells, PI3K = phosphoinositide 3-kinase, RNA = ribonucleic acid, TGF = transforming growth factor, TNF = tumour necrosis factor.</p><p>Note:– Genes names are those assigned by the HUGO gene nomenclature committee.</p

    Network representation of genes differentially expressed in melioidosis.

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    <p>‘Canonical’ pathways (such as those presented in a standard biochemistry textbook) are manually curated collections of protein interactions arranged in a manner that aids human understanding, and as artificial constructs the boundaries between pathways are subjective. Pathways that are conceptually distinct often have proteins in common and overlap, so in modular analysis, multiple pathways may collapse into a single module, causing other pathways and relationships to gain prominence. These two networks (<b>A</b> and <b>B</b>) represent those genes that are differentially expressed in melioidosis. For simplicity of presentation, we have used only a subset of genes in these networks. The top 221 upregulated genes (as ranked by <i>p</i>-value) are presented in <b>A</b>, and the top 155 downregulated genes are in <b>B</b>. The same clusters were found in an analysis of the whole gene set and those results are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054961#pone-0054961-t002" target="_blank">Tables 2</a> & <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054961#pone-0054961-t003" target="_blank">3</a>. <b>Network </b><b>A</b>. IFN-γ, TNF-α, IL-12 signalling pathways cluster together with the glypican network in the centre of the graph, but the complement/chemokine receptor (<b>cluster 1</b>), inflammasome (<b>cluster 2</b>) and Toll-like receptor pathways come to prominence in this analysis (<b>cluster 3</b>). <b>Network B</b>. IFN-γ, TGF-β and TNF signalling again cluster in the middle of the network. The two most prominent clusters are ribosomal proteins (<b>cluster 1</b>) and zinc finger proteins (<b>cluster 2</b>).</p

    The 86-gene signature of tuberculosis is also seen in melioidosis.

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    <p>These heat maps demonstrate the gene expression profiles for two cohorts: (A) melioidosis and (B) tuberculosis. The 86 genes displayed are those identified by Berry <i>et al. </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054961#pone.0054961-Berry1" target="_blank">[7]</a> as being specific for tuberculosis, after excluding genes differentially regulated in other infections (<i>Staphylococcus aureus</i> and Group A Streptococcus) and inflammatory conditions (adult onset Still’s disease and systemic lupus erythematosus). Each column in the heat map is the gene expression profile of an individual, with control subjects on the left and patients on the right. Each cell within the heat map is the expression of a single gene: orange genes are upregulated and purple genes are downregulated, with expression normalized across the rows. We used this 86-gene signature to cluster study participants into two groups (marked black and red in the coloured banner at the top of each heat map). In the tuberculosis cohort, three controls clustered with the patients, and two patients clustered with the controls. In the melioidosis cohort, the same 86-gene signature also allowed us to distinguish controls and patients, with the exception of four patients who clustered with the controls. Despite the same microarray platform being used, the two cohorts were assayed as separate batches, so the absolute fluorescence intensities are different, making a direct comparison of melioidosis and tuberculosis impossible. All patients were therefore compared to their own controls.</p

    Interferon signatures for melioidosis and tuberculosis.

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    <p>Note: The interferon signatures for melioidosis (<b>A</b>) and tuberculosis (<b>B</b>) are listed here (analysis from <a href="http://www.interferome.org" target="_blank">www.interferome.org</a>). Berry <i>et al.</i> noted that both type 1 and type 2 interferon responses were prominent in tuberculosis. We find that type 1 interferon responses appear in melioidosis also.</p

    Patient characteristics.

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    a<p>One patient in this group was lost to follow-up following discharge from hospital, and was counted as having survived to discharge.</p><p>Gb = Glibenclamide. Values reported are means, except where stated.</p

    Image_2_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.jpeg

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    IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p

    Table_1_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.xlsx

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    IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p

    Image_4_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.jpeg

    No full text
    IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p
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