ORCID Profile
0000-0003-0531-5426
Current Organisation
University of Oxford
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Publisher: Elsevier BV
Date: 03-2021
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2020-037358
Abstract: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. The ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci hyperinvasive meningococci all meningococci those meningococci expressing vaccine antigens and other Neisseria spp. A s le size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055) the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. ISRCTN75858406 Pre-results, EudraCT 2017-004609-42.
Publisher: Elsevier BV
Date: 12-2020
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/BMJOPEN-2018-028578
Abstract: The POInT study, an investigator initiated, randomised, placebo-controlled, double-blind, multicentre primary prevention trial is conducted to determine whether daily administration of oral insulin, from age 4.0 months to 7.0 months until age 36.0 months to children with elevated genetic risk for type 1 diabetes, reduces the incidence of beta-cell autoantibodies and diabetes. Infants aged 4.0 to 7.0 months from Germany, Poland, Belgium, UK and Sweden are eligible if they have a .0% expected risk for developing multiple beta-cell autoantibodies as determined by genetic risk score or family history and human leucocyte antigen genotype. Infants are randomised 1:1 to daily oral insulin (7.5 mg for 2 months, 22.5 mg for 2 months, 67.5 mg until age 36.0 months) or placebo, and followed for a maximum of 7 years. Treatment and follow-up is stopped if a child develops diabetes. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies or diabetes. Other outcomes are: (1) Any persistent confirmed beta-cell autoantibody (glutamic acid decarboxylase (GADA), IA-2A, autoantibodies to insulin (IAA) and zinc transporter 8 or tetraspanin 7), or diabetes, (2) Persistent confirmed IAA, (3) Persistent confirmed GADA and (4) Abnormal glucose tolerance or diabetes. The study is approved by the ethical committees of all participating clinical sites. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the trial. NCT03364868 .
Publisher: BMJ
Date: 16-06-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
Publisher: American Medical Association (AMA)
Date: 09-01-2008
Abstract: Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. To determine the immunogenicity of a novel tetravalent CRM(197)-conjugated meningococcal vaccine (MenACWY) in infants. Randomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006. UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Percentage of infants with a human complement serum bactericidal activity (hSBA) titer >or=1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed. According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers >or=1:4 after primary immunization were serogroup A, 93% (84%-98%) C, 96% (89%-99%) W-135, 97% (90%-100%) and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%) C, 98% (92%-100%) W-135, 99% (93%-100%) and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%) C, 98% (93%-99%) W-135, 99% (94%-100%) and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients a temperature of 38 degrees C or greater was observed in 4% and 2% in these groups, respectively. MenACWY is well tolerated and immunogenic in infancy. Trial Registration clinicaltrials.gov Identifier: NCT00262002.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Elsevier BV
Date: 04-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
Publisher: Elsevier BV
Date: 08-2020
Publisher: American Society for Microbiology
Date: 28-12-2011
DOI: 10.1128/CVI.05379-11
Abstract: The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between in iduals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old mean time after vaccination, 8 months). In iduals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study ( P , 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) ( P = 0.004 [unadjusted]) and CD44 (rs12419062) ( P = 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
Publisher: Massachusetts Medical Society
Date: 30-07-2020
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 31-03-2009
Publisher: Oxford University Press (OUP)
Date: 23-07-2020
Abstract: Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory s les, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between 2 RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development. Clinical Trials Registration. NCT03627572 and NCT03756766.
Publisher: American Society for Clinical Investigation
Date: 17-10-2022
DOI: 10.1172/JCI162123
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Matthew Snape.