Andrew J Pollard

NIHR Oxford Biomedical Research, Oxford, England, United Kingdom

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Publications (323)2083.73 Total impact

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    Christoph J Blohmke · Daniel O'Connor · Andrew J Pollard ·
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    ABSTRACT: Editorial summary High-throughput technologies applied to the analysis of vaccine responses are likely to reveal the mechanisms responsible for vaccine-induced protection, aid understanding of vaccine safety and help accelerate vaccine development and clinical trials.
    Genome Medicine 11/2015; 7(1):114. DOI:10.1186/s13073-015-0236-1 · 5.34 Impact Factor
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    ABSTRACT: The Raman scattering D-peak in graphene is spatially localised in close proximity to defects. Here, we demonstrate the capability of tip-enhanced Raman spectroscopy (TERS) to probe individual point defects, even for a graphene layer with an extremely low defect density. This is of practical interest for future graphene electronic devices. The measured TERS spectra enable a direct determination of the average inter-defect distance within the graphene sheet. Analysis of the TERS enhancement factor of the graphene Raman peaks highlights the preferential enhancement and symmetry-dependent selectivity of the D-peak intensity caused by zero-dimensional Raman scatterers.
    Nanoscale 11/2015; 7(46). DOI:10.1039/c5nr04664e · 7.39 Impact Factor
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    Malick M. Gibani · Celina Jin · Thomas C. Darton · Andrew J. Pollard ·

    Clinical Infectious Diseases 11/2015; 61(suppl 4):S266-S271. DOI:10.1093/cid/civ673 · 8.89 Impact Factor
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    PLoS ONE 10/2015; 10(10):e0140345. DOI:10.1371/journal.pone.0140345 · 3.23 Impact Factor

  • BMJ Open 10/2015; 5(10):e008748. DOI:10.1136/bmjopen-2015-008748 · 2.27 Impact Factor
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    ABSTRACT: High-throughput sequencing of the B cell receptor (BCR) repertoire can provide rapid characterization of the B cell response in a wide variety of applications in health, after vaccination and in infectious, inflammatory and immune-driven disease, and is starting to yield clinical applications. However, the interpretation of repertoire data is compromised by a lack of studies to assess the intra and inter-individual variation in the BCR repertoire over time in healthy individuals. We applied a standardized isotype-specific BCR repertoire deep sequencing protocol to a single highly sampled participant, and then evaluated the method in 10 further participants to comprehensively describe such variation. We assessed total repertoire metrics of mutation, diversity, VJ gene usage and isotype subclass usage, as well as tracking specific BCR sequence clusters. There was good assay reproducibility (both in PCR amplification and biological replicates), but we detected striking fluctuations in the repertoire over time that we hypothesize may be due to subclinical immune activation. Repertoire properties were unique for each individual, which could partly be explained by a decrease in IgG2 with age, and genetic differences at the immunoglobulin locus. There was a small repertoire of public clusters (0.5, 0.3 and 1.4% of total IgA, IgG and IgM clusters respectively), which was enriched for expanded clusters containing sequences with suspected specificity towards antigens that should have been historically encountered by all participants through prior immunization or infection. We thus provide baseline BCR repertoire information that can be used to inform future study design, and aid in interpretation of results from these studies. Furthermore our results indicate that BCR repertoire studies could be used to track changes in the public repertoire in and between populations that might relate to population immunity against infectious diseases, and identify the characteristics of inflammatory and immunological diseases.
    Frontiers in Immunology 09/2015; 6:531. DOI:10.3389/fimmu.2015.00531

  • Public Health Ethics 09/2015; DOI:10.1093/phe/phv026 · 1.18 Impact Factor
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    ABSTRACT: Background: Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/principal findings: Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/significance: We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi.
    PLoS Neglected Tropical Diseases 09/2015; 9(9):e0004029. DOI:10.1371/journal.pntd.0004029 · 4.45 Impact Factor
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    ABSTRACT: Following the introduction of effective protein-polysaccharide conjugate vaccines against capsular group C meningococcal disease in Europe, meningococci of capsular group B remain a major cause of death and can result in debilitating sequelae. The outer membrane proteins PorA and FetA have previously been shown to induce bactericidal antibodies in humans. Despite considerable antigenic variation among PorA and FetA OMPs in meningococci, systematic molecular epidemiological studies revealed this variation is highly structured so that a limited repertoire of antigenic types is congruent with the hyperinvasive meningococcal lineages that have caused most of the meningococcal disease in Europe in recent decades. Here we describe the development of a prototype vaccine against capsular group B meningococcal infection based on a N. meningitidis isolate genetically engineered to have constitutive expression of the outer membrane protein FetA. Deoxycholate outer membrane vesicles (dOMVs) extracted from cells cultivated in modified Frantz medium contained 21.8% PorA protein, 7.7% FetA protein and 0.03 μg LPS per μg protein (3%). The antibody response to the vaccine was tested in three mouse strains and the toxicological profile of the vaccine was tested in New Zealand white rabbits. Administration of the vaccine, MenPF-1, when given by intramuscular injection on 4 occasions over a 9 week period, was well tolerated in rabbits up to 50 μg/dose, with no evidence of systemic toxicity. These data indicated that the MenPF-1 vaccine had a toxicological profile suitable for testing in a phase I clinical trial.
    PLoS ONE 09/2015; 10(9):e0134353. DOI:10.1371/journal.pone.0134353 · 3.23 Impact Factor
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    ABSTRACT: Admission of infants to hospital with bronchiolitis consumes considerable healthcare resources each winter. We report an analysis of hospital admissions in England over five decades. Data were analysed from the Hospital In-Patient Enquiry (HIPE, 1968-1985), Hospital Episode Statistics (HES, 1989-2011), Oxford Record Linkage Study (ORLS, 1963-2011) and Paediatric Intensive Care Audit Network (PICANet, 2003-2012). Cases were identified using International Classification of Diseases (ICD) codes in discharge records. Bronchiolitis was given a separate code in ICD9 (used in England from 1979). Geographical variation was analysed using Local Authority area boundaries. Maternal and perinatal risk factors associated with bronchiolitis and subsequent admissions for asthma were analysed using record-linkage. All-England HIPE and HES data recorded 468 138 episodes of admission for bronchiolitis in infants aged <1 year between 1979 and 2011. In 2011 the estimated annual hospital admission rate was 46.1 (95% CI 45.6 to 46.6) per 1000 infants aged <1 year. Between 2004 and 2011 the rates rose by an average of 1.8% per year in the all-England HES data, whereas admission rates to paediatric intensive care changed little (1.3 to 1.6 per 1000 infants aged <1 year). A fivefold geographical variation in hospital admission rates was observed. Young maternal age, low social class, low birth weight and maternal smoking were among factors associated with an increased risk of hospital admission with bronchiolitis. Hospital admissions for infants with bronchiolitis have increased substantially in recent years. However, cases requiring intensive care have changed little since 2004. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Archives of Disease in Childhood 09/2015; DOI:10.1136/archdischild-2015-308723 · 2.90 Impact Factor
  • 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:
    Journal of Public Health 08/2015; DOI:10.1093/pubmed/fdv112 · 2.04 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 · 15.84 Impact Factor
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    ABSTRACT: Since the discovery of graphene, organic surface contamination has posed difficulties both for accurate characterization of the material's intrinsic properties and for development of graphene devices. In this study, we investigate the use of a mass-selected argon gas cluster ion beam for removing organic contaminants, such as residual poly(methyl methacrylate) (PMMA), from single-layer graphene. The influence of cluster ion size, energy, and ion dose has been investigated to identify the important factors for minimizing damage to the graphene layer during the cleaning process. Raman spectroscopy was used to analyze the variation in the D-peak and G-peak intensity ratio, an indicator of damage to the graphene lattice, as a function of ion beam dose and kinetic energy per atom (E/n) in the cluster ions. Using a mass-selected 5 keV Ar5000 beam with a dose of 5.0 ions/nm2, we were able to demonstrate removal of polymer residue and other carbonaceous material from single-layer chemical vapor deposition (CVD)-grown graphene while minimizing the damage to the graphene itself. This demonstrates that the mass-selected argon cluster ion beam is a suitable, industry-relevant technology for use in large scale production of commercially desirable CVD-grown graphene.
    The Journal of Physical Chemistry C 07/2015; 119(31):150722062304007. DOI:10.1021/acs.jpcc.5b03144 · 4.77 Impact Factor
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    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; 33(36). DOI:10.1016/j.vaccine.2015.06.105 · 3.62 Impact Factor
  • Helen Marshall · Bing Wang · Steve Wesselingh · Matthew Snape · Andrew J Pollard ·
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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
  • Alexander J Mentzer · Daniel O'Connor · Andrew J Pollard · Adrian V S Hill ·
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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 · 7.06 Impact Factor
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    ABSTRACT: Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.
    PLoS ONE 06/2015; 10(6):e0129555. DOI:10.1371/journal.pone.0129555 · 3.23 Impact Factor

Publication Stats

6k Citations
2,083.73 Total Impact Points


  • 2012-2015
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 2003-2015
    • Oxford University Hospitals NHS Trust
      • Department of Paediatrics
      Oxford, England, United Kingdom
  • 2001-2015
    • University of Oxford
      • • Department of Paediatrics
      • • Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
      Oxford, 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
  • 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
  • 2002
    • Sheffield Children's NHS Foundation Trust
      Sheffield, 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
  • 1996-1999
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom