Andrew J Pollard

NIHR Oxford Biomedical Research, Oxford, England, United Kingdom

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Publications (307)1976.58 Total impact

  • Karen J Ford · Sarah Lang · Andrew J Pollard · Noel D McCarthy
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    ABSTRACT: Immunization advice services can support health professionals by providing rapid access to accurate and reliable current information and advice. The Vaccine Advice for Clinicians Service (VACCSline) is a service for health professionals working within the Thames Valley Area of the UK. We reviewed all 4299 enquiries received by VACCSline over 3 years. Queries were summarized by vaccine type and topic of enquiry. Associations with profession and workplace of the enquirer were tested using Fisher's exact tests. Incomplete immunization status and non-UK schedules were the most common topics of enquiry. Practice nurses were the main service users followed by doctors. Enquiries varied by professional role. Alterations to the immunization programme led to temporary changes to enquiry content and some more persistent adjustments in the balance of enquiries were identified, such as an increase in enquiries relating to vaccination in pregnancy. The content of enquiries to VACCSline is broad, confirming the need for immunizers to have a wide knowledge base and access to specialist advice to assist with complex scenarios. Systematic data capture provided intelligence to guide training and materials to support immunizers. A wider networked application of this approach could improve support for immunizers. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Journal of Public Health 08/2015; DOI:10.1093/pubmed/fdv112 · 2.30 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication-defective viral vectors encoding the RSV fusion (F), nucleocapsid (N), and matrix (M2-1) proteins for the induction of humoral and cellular responses. We performed an open-label, dose escalation, phase 1 clinical trial in 42 healthy adults in which four different combinations of prime/boost vaccinations were investigated for safety and immunogenicity, including both intramuscular (IM) and intranasal (IN) administration of the adenovirus-vectored vaccine. The vaccines were safe and well tolerated, with the most common reported adverse events being mild injection site reactions. No vaccine-related serious adverse events occurred. RSV neutralizing antibody titers rose in response to IM prime with PanAd3-RSV and after IM boost for individuals primed by the IN route. Circulating anti-F immunoglobulin G (IgG) and IgA antibody-secreting cells (ASCs) were observed after the IM prime and IM boost. RSV-specific T cell responses were increased after the IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. Interferon-γ (IFN-γ) secretion after boost was from both CD4(+) and CD8(+) T cells, without detectable T helper cell 2 (TH2) cytokines that have been previously associated with immune pathogenesis following exposure to RSV after the formalin-inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 08/2015; 7(300):300ra126. DOI:10.1126/scitranslmed.aac5745 · 14.41 Impact Factor
  • T John · M Voysey · L.M. Yu · N McCarthy · M Baudin · P Richard · A Fiquet · N Kitchin · A.J. Pollard
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    ABSTRACT: This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 07/2015; DOI:10.1016/j.vaccine.2015.06.105 · 3.49 Impact Factor
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    ABSTRACT: Neisseria meningitidis still leads to deaths and severe disability in children, adolescents and adults. Six different capsular groups of N. meningitidis cause invasive meningococcal disease in the form of meningitis and septicaemia in humans. Although conjugate meningococcal vaccines have been developed to provide protection against four of the capsular groups causing most diseases in humans, vaccines against capsular group B, which causes 85% of cases in Australia and the United Kingdom, have only recently been developed. A capsular group B meningococcal vaccine - 4CMenB (Bexsero) - has recently been licensed in the European Union, Canada and Australia. In Australia, a submission for inclusion of 4CMenB in the funded national immunization programme has recently been rejected. The vaccine will now be introduced into the national immunization programme in the United Kingdom following negotiation of a cost-effective price. With the current low incidence of invasive meningococcal disease in many regions, cost-effectiveness of a new capsular group B meningococcal vaccine is borderline in both the United Kingdom and Australia. Cost-effectiveness of an infant programme is determined largely by the direct protection of those vaccinated and is driven by the higher rate of disease in this age group. However, for an adolescent programme to be cost-effective, it must provide both long-term protection against both disease and carriage. The potential of vaccination to reduce the rate of severe invasive disease is a real possibility. A dual approach using both an infant and adolescent immunization programme to provide direct protection to those age groups at highest risk of meningococcal disease and to optimize the potential herd immunity effects is likely to be the most effective means of reducing invasive meningococcal disease. This commentary aims to describe the known disease burden and consequences of meningococcal disease, and the development and potential effectiveness of new capsular group B meningococcal vaccines.
    International Journal of Evidence-Based Healthcare 06/2015; DOI:10.1097/XEB.0000000000000048
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    PLoS ONE 06/2015; 10(6):e0129555. DOI:10.1371/journal.pone.0129555 · 3.23 Impact Factor
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    ABSTRACT: Vaccines have revolutionized modern public health. The effectiveness of some vaccines is limited by the variation in response observed between individuals and across populations. There is compelling evidence that a significant proportion of this variability can be attributed to human genetic variation, especially for those vaccines administered in early life. Identifying and understanding the determinants of this variation could have a far-reaching influence upon future methods of vaccine design and deployment. In this review, we summarize the genetic studies that have been undertaken attempting to identify the genetic determinants of response heterogeneity for the vaccines against hepatitis B, measles and rubella. We offer a critical appraisal of these studies and make a series of suggestions about how modern genetic techniques, including genome-wide association studies, could be used to characterize the genetic architecture of vaccine response heterogeneity. We conclude by suggesting how the findings from such studies could be translated to improve vaccine effectiveness and target vaccination in a more cost-effective manner. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
    Philosophical Transactions of The Royal Society B Biological Sciences 06/2015; 370(1671). DOI:10.1098/rstb.2014.0341 · 6.31 Impact Factor
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    ABSTRACT: This study will develop the first human challenge model of paratyphoid infection which may then be taken forward to evaluate paratyphoid vaccine candidates. Salmonella Paratyphi A is believed to cause a quarter of the estimated 20 million cases of enteric fever annually. Epidemiological evidence also suggests that an increasing proportion of the enteric fever burden is attributable to S. Paratyphi infection meriting further attention and interest in vaccine development. Assessment of paratyphoid vaccine efficacy in preclinical studies is complicated by the lack of a small animal model and the human-restricted nature of the infection. The use of experimental human infection in healthy volunteers provides an opportunity to address these problems in a cost-effective manner. Volunteers will ingest virulent S. Paratyphi A bacteria (NVGH308 strain) with a bicarbonate buffer solution to establish the infectious dose resulting in an 'attack rate' of 60-75%. Using an a priori decision-making algorithm, the challenge dose will be escalated or de-escalated to achieve the target attack rate, with the aim of reaching the study end point while exposing as few individuals as possible to infection. The attack rate will be determined by the proportion of paratyphoid infection in groups of 20 healthy adult volunteers, with infection being defined by one or more positive blood cultures (microbiological end point) and/or fever, defined as an oral temperature exceeding 38°C sustained for at least 12 h (clinical end point); 20-80 participants will be required. Challenge participants will start a 2-week course of an oral antibiotic on diagnosis of infection, or after 14 days follow-up. The strict eligibility criterion aims to minimise risk to participants and their close contacts. Ethical approval has been obtained. The results will be disseminated in a peer-reviewed journal and presented at international congresses. NCT02100397. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    BMJ Open 06/2015; 5(6):e007481. DOI:10.1136/bmjopen-2014-007481 · 2.06 Impact Factor
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    ABSTRACT: A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48h and 96h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.
    PLoS Neglected Tropical Diseases 06/2015; 9(6):e0003837. DOI:10.1371/journal.pntd.0003837 · 4.49 Impact Factor
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    ABSTRACT: Since the 18th century a wealth of knowledge regarding infectious disease pathogenesis, prevention, and treatment has been accumulated from findings of infection challenges in human beings. Partly because of improvements to ethical and regulatory guidance, human challenge studies-involving the deliberate exposure of participants to infectious substances-have had a resurgence in popularity in the past few years, in particular for the assessment of vaccines. To provide an overview of the potential use of challenge models, we present historical reports and contemporary views from experts in this type of research. A range of challenge models and practical approaches to generate important data exist and are used to expedite vaccine and therapeutic development and to support public health modelling and interventions. Although human challenge studies provide a unique opportunity to address complex research questions, participant and investigator safety is paramount. To increase the collaborative effort and future success of this area of research, we recommend the development of consensus frameworks and sharing of best practices between investigators. Furthermore, standardisation of challenge procedures and regulatory guidance will help with the feasibility for using challenge models in clinical testing of new disease intervention strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Infectious Diseases 05/2015; 15(7). DOI:10.1016/S1473-3099(15)00068-7 · 19.45 Impact Factor
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    ABSTRACT: Next-generation sequencing was used to investigate the B cell receptor heavy chain transcript repertoire of different B cell subsets (naïve, marginal zone, IgM memory and IgG memory) at baseline, and of plasma cells 7 days following administration of serogroup ACWY meningococcal polysaccharide and protein-polysaccharide conjugate vaccines. Baseline B cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germ-line and complementarity-determining region 3 length) that were conserved between individuals. However, analyzing the complementarity-determining region 3 amino acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 plasma cells demonstrated nearly tenfold greater sequence sharing between individuals than the baseline subsets, consistent with the plasma cells being induced by the vaccine antigen, and sharing specificity for a more limited range of epitopes. By annotating plasma cell sequences based on IgG subclass usage and mutation, and also comparing them to the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate vaccines. Plasma cells produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the plasma cells were predominantly IgG2, less mutated, and were equally likely to be related to marginal zone, IgM memory or IgG memory cells. High-throughput B cell repertoire sequencing thus provides a unique insight into patterns of B cell activation not possible from more conventional measures of immunogenicity.Immunology and Cell Biology accepted article preview online, 15 May 2015. doi:10.1038/icb.2015.57.
    Immunology and Cell Biology 05/2015; DOI:10.1038/icb.2015.57 · 4.21 Impact Factor
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    ABSTRACT: Outer membrane vesicle (OMV) vaccines are used against outbreaks of capsular group B Neisseria meningitidis (MenB) caused by strains expressing particular PorA outer membrane proteins (OMP). Ferric enterobactin receptor (FetA) is another variable OMP that induces type-specific bactericidal antibodies, and the combination of judiciously chosen PorA and FetA variants in vaccine formulations is a potential approach to broaden protection of such vaccines. The OMV vaccine MenPF-1 was generated by genetically modifying N. meningitidis strain 44/76 to constitutively express FetA. Three doses of 25μg or 50μg of MenPF-1 were delivered intramuscularly to 52 healthy adults. MenPF-1 was safe and well tolerated. Immunogenicity was measured by serum bactericidal assay (SBA) against wild-type and isogenic mutant strains. After 3 doses, the proportion of volunteers with SBA titres ≥ 1:4 (the putative protective titre) was 98% for the wild-type strain, and 77% for the strain 44/76 FetAonPorAoff compared to 51% in the strain 44/76 FetAoffPorAoff, demonstrating that vaccination with MenPF-1 simultaneously induced FetA and PorA bactericidal antibodies. This study provides a proof-of-concept for generating bactericidal antibodies against FetA after OMV vaccination in humans. Prevalence-based choice of PorA and FetA types can be used to formulate a vaccine for broad protection against MenB disease. Copyright © 2015. Published by Elsevier Ltd.
    The Journal of infection 05/2015; 15. DOI:10.1016/j.jinf.2015.05.006 · 4.02 Impact Factor
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    ABSTRACT: We determine the effect of defects induced by ion bombardment on the Raman spectrum of single-layer molybdenum disulfide. The evolution of both the linewidths and frequency shifts of the first-order Raman bands with the density of defects is explained with a phonon confinement model, using density functional theory to calculate the phonon dispersion curves. We identify several defect-induced Raman scattering peaks arising from zone-edge phonon modes. Among these, the most prominent is the LA(M) peak at ∼227cm−1 and its intensity, relative to the one of first-order Raman bands, is found to be proportional to the density of defects. These results provide a practical route to quantify defects in single-layer MoS2 using Raman spectroscopy and highlight an analogy between the LA(M) peak in MoS2 and the D peak in graphene.
    Physical Review B 05/2015; 91(19). DOI:10.1103/PhysRevB.91.195411 · 3.74 Impact Factor
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    ABSTRACT: Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg) by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD) and those who were not (No TD). TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1). We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.
    PLoS Pathogens 05/2015; 11(5):e1004914. DOI:10.1371/journal.ppat.1004914 · 8.06 Impact Factor
  • Simon B. Drysdale · Andrew J. Pollard
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    ABSTRACT: Capsular group B Neisseria meningitidis is one of the leading causes of death in developed countries. A new vaccine (4CMenB) has recently been developed which was found to have an acceptable safety profile in clinical studies and to be immunogenic. This review examines the evidence supporting the licensure of the 4CMenB vaccine and discusses recommendations for its use. Copyright © 2015. Published by Elsevier Ltd.
    The Journal of infection 04/2015; 71. DOI:10.1016/j.jinf.2015.04.021 · 4.02 Impact Factor
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    ABSTRACT: To determine whether the immunogenicity of a single dose infant priming schedule of serogroup C meningococcal (MenC) conjugate vaccine is non-inferior to a two dose priming schedule when followed by a booster dose at age 12 months. Phase IV open label randomised controlled trial carried out from July 2010 until August 2013 SETTING: Four centres in the United Kingdom and one centre in Malta. Healthy infants aged 6-12 weeks followed up until age 24 months. In the priming phase of the trial 509 infants were randomised in a 10:10:7:4 ratio into four groups to receive either a single MenC-cross reacting material 197 (CRM) dose at 3 months; two doses of MenC-CRM at 3 and 4 months; a single MenC-polysaccharide-tetanus toxoid (TT) dose at 3 months; or no MenC doses, respectively. Haemophilus influenzae type b (Hib)-MenC-TT vaccine was administered to all infants at 12 months of age. All infants also received the nationally routinely recommended vaccines. Blood samples were taken at age 5, 12, 13, and 24 months. MenC serum bactericidal antibody assay with rabbit complement (rSBA) one month after the Hib-MenC-TT vaccine. Non-inferiority was met if the lower 95% confidence limit of the difference in the mean log10 MenC rSBA between the single dose MenC-CRM and the two dose MenC-CRM groups was >-0.35. The primary objective was met: after a Hib-MenC-TT booster dose at 12 months of age the MenC rSBA geometric mean titres induced in infants primed with a single MenC-CRM dose were not inferior to those induced in participants primed with two MenC-CRM doses in infancy (660 (95% confidence interval 498 to 876) v 295 (220 to 398)) with a corresponding difference in the mean log10 MenC rSBA of 0.35 (0.17 to 0.53) that showed superiority of the single over the two dose schedule). Exploration of differences between the priming schedules showed that one month after Hib-MenC-TT vaccination, MenC rSBA ≥1:8 was observed in >96% of participants previously primed with any of the MenC vaccine schedules in infancy and in 83% of those who were not vaccinated against MenC in infancy. The MenC rSBA geometric mean titres induced by the Hib-MenC-TT boost were significantly higher in children who were primed with one rather than two MenC-CRM doses in infancy. Only priming with MenC-TT, however, induced robust MenC bactericidal antibody after the Hib-MenC-TT booster that persisted until 24 months of age. MenC vaccination programmes with two MenC infant priming doses could be reduced to a single priming dose without reducing post-boost antibody titres. When followed by a Hib-MenC-TT booster dose, infant priming with a single MenC-TT vaccine dose induces a more robust antibody response than one or two infant doses of MenC-CRM. Bactericidal antibody induced by a single Hib-MenC-TT conjugate vaccine dose at 12 months of age (that is, a toddler only schedule), without infant priming, is not well sustained at 24 months. Because of rapid waning of MenC antibody, programmes using toddler only schedules will still need to rely on herd protection to protect infants and young children.Trial registration Eudract No: 2009-016579-31; NCT01129518; study ID: 2008_06 (http://clinicaltrials.gov). © Pace et al 2015.
    BMJ (online) 04/2015; 350(apr01 16):h1554. DOI:10.1136/bmj.h1554 · 16.38 Impact Factor
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    ABSTRACT: Injections with hypodermic needle and syringe (HNS) are the current standard of care globally, but the use of needles is not without limitation. While a plethora of needle-free injection devices exist, vaccine reformulation is costly and presents a barrier to their widespread clinical application. To provide a simple, needle-free, and broad-spectrum protein antigen delivery platform, we developed novel potassium-doped hydroxyapatite (K-Hap) microparticles with improved protein loading capabilities that can provide sustained local antigen presentation and release. K-Hap showed increased protein adsorption over regular hydroxyapatite (p < 0.001), good structural retention of the model antigen (CRM197) with 1% decrease in α-helix and no change in β-sheet content upon adsorption, and sustained release in vitro. Needle-free intradermal powder inoculation with K-Hap-CRM197 induced significantly higher IgG1 than IgG2a geometric mean titers (GMT) in a BALB/c mouse model (p<0.001), and induced IgG titer levels that were not different from the current clinical standard (p > 0.05), namely alum adsorbed CRM197 by IM delivery. The presented results suggest that K-Hap microparticles may be used as a novel needle-free delivery vehicle for some protein antigens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Clinical and vaccine Immunology: CVI 03/2015; 22(5). DOI:10.1128/CVI.00121-15 · 2.37 Impact Factor
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    ABSTRACT: The multicomponent serogroup B meningococcal (4CMenB) vaccine induces antibodies against indicator strains of serogroup B meningococcus under various schedules. We investigated the persistence of antibodies in 5-year-old children 18-20 months after their last dose (at about 3.5 years of age). We assessed 5-year-old children who received the 4CMenB vaccine in a previous randomized trial. We also recruited 50 vaccinenaive 5-year-olds and administered 2 doses of 4CMenB to each child. We measured serum bactericidal antibody titres against 4 indicator strains of serogroup B meningococcus matched to each individual vaccine component and against 4 mismatched strains. Of those who received the 4CMenB vaccine at 2, 4, 6, 12 and 40 months (n = 16), the percentage with protective antibody titres (≥ 1:4) at 60 months ranged from 44% to 88% against matched strains and from 13% to 81% against mismatched strains. Loss of protective titres was also observed for those who received the 4CMenB vaccine at 12, 40 and 42 months (n = 5) (80%-100% against matched strains, 60%-100% against mismatched strains) or at 40 and 42 months (n = 29) (31%-100% against matched strains, 41%-81% against mismatched strains). Administering the 4CMenB vaccine to 5-year-old children yielded protective titres against matched strains in 92%-100% and against mismatched strains in 59%-100%. The majority of these children reported injectionsite pain (40/50 [80%] after dose 1, 39/46 [85%] after dose 2) and erythema (47/50 [94%] and 40/46 [87%], respectively); rates of fever were low (5/50 [10%] and 2/46 [4%], respectively). Waning of immunity by 5 years of age occurred after receipt of the 4CMenB vaccine in infancy, even with an additional booster at 40 months. The 4CMenB vaccine is immunogenic and was fairly well tolerated by 5 year-old children, although injection-site pain was noteworthy. Clinical Trials.gov, no. NCT01027351. © 8872147 Canada Inc.
    Canadian Medical Association Journal 03/2015; 187(7). DOI:10.1503/cmaj.141200 · 5.81 Impact Factor
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    ABSTRACT: Recent development of serogroup B meningococcal (MenB) vaccines highlights the importance of pharyngeal carriage data, particularly in adolescents and young adults, to inform implementation strategies. We describe current UK carriage prevalence in this high risk population and compare methods of carriage detection. In this multisite study, pharyngeal swabs were collected on 3-4 occasions over 6-12 months, from 1040 school and university students, aged 10-25 years. Meningococcal carriage was detected by standard culture combined with seroagglutination or PCR of cultured isolates, or by direct PCR from swab. The factor H binding protein (fHBP) variants present in meningococcal isolates were determined. Meningococcal serogroups B and Y were most common, with carriage up to 6.5% and 5.5% respectively, increasing throughout adolescence. Identification by seroagglutination was often unreliable, and the sensitivity of direct PCR detection was 66% compared to culture combined with PCR. Of MenB isolates, 89.1% had subfamily A variants of fHBP. The acquisition rate of MenB carriage was estimated at 2.8 per 1000 person-months. If vaccination is to precede the adolescent rise in MenB carriage, these data suggest it should take place in early adolescence. Studies assessing vaccine impact should use molecular methods to detect carriage. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Infection 02/2015; 55(1). DOI:10.1016/j.jinf.2015.02.006 · 4.02 Impact Factor
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    ABSTRACT: Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immu nisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood.
    The Lancet Infectious Diseases 02/2015; · 19.45 Impact Factor
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    ABSTRACT: Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood.
    The Lancet Infectious Diseases 02/2015; 15(4). DOI:10.1016/S1473-3099(15)70007-1 · 19.45 Impact Factor

Publication Stats

5k Citations
1,976.58 Total Impact Points

Institutions

  • 2012–2015
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 2003–2015
    • University of Oxford
      • • Department of Paediatrics
      • • Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
      Oxford, England, United Kingdom
  • 2002–2015
    • Oxford University Hospitals NHS Trust
      • Department of Paediatrics
      Oxford, England, United Kingdom
    • Sheffield Children's NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 2014
    • National Physical Laboratory
      Londinium, England, United Kingdom
  • 2013
    • University of Melbourne
      • Department of Paediatrics
      Melbourne, Victoria, Australia
  • 2011
    • The University of Manchester
      • Faculty of Life Sciences
      Manchester, England, United Kingdom
  • 2007
    • Sanofi Pasteur MSD
      Lyons, Rhône-Alpes, France
  • 2003–2006
    • University of Leicester
      Leiscester, England, United Kingdom
  • 2005
    • KEMRI-Wellcome Trust Research Programme
      Kilifi, Kilifi, Kenya
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia
  • 2001–2004
    • Children's & Women's Health Centre of British Columbia
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
  • 1999–2003
    • Imperial College London
      • • Faculty of Medicine
      • • Section of Paediatrics
      London, ENG, United Kingdom
    • National Institute for Public Health and the Environment (RIVM)
      Utrecht, Utrecht, Netherlands
    • University of Leeds
      Leeds, England, United Kingdom
  • 2000–2002
    • University of British Columbia - Vancouver
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
    • British Columbia Medical Association
      Vancouver, British Columbia, Canada
  • 1997–1999
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom