Andrew J Pollard

NIHR Oxford Biomedical Research, Oxford, England, United Kingdom

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Publications (247)1515.87 Total impact

  • Nigel Curtis, Andrew J. Pollard, Adam Finn
    Journal of Infection. 10/2014;
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    ABSTRACT: Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.
    Archives of disease in childhood. 09/2014;
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 07/2014;
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    ABSTRACT: Meningococcal conjugate vaccines are today successfully deployed in universal programmes for children and adolescents in different geographic regions to control meningitis and septicaemia. However, in adults, the advantages of these conjugates over the older polysaccharide vaccines are less clear. In this randomised clinical trial, we demonstrate that both conjugate and polysaccharide quadrivalent meningococcal vaccines elicit protective antibody responses in adults aged 18-70. This study is registered at www.clinicaltrials.gov NCT00901940.
    Clinical and vaccine Immunology: CVI 06/2014; · 2.60 Impact Factor
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    ABSTRACT: The ELISpot assay is used in vaccine studies for the quantification of antigen-specific memory B cells (BMEM), and can be performed using cryopreserved samples. The effects of cryopreservation on BMEM detection and the consistency of cultured ELISpot assays when performed by different operators or laboratories are unknown. In this study, blood was taken from healthy volunteers, and a cultured ELISpot assay was used to count BMEM specific for 2 routine vaccine antigens (diphtheria and tetanus toxoid). Results were assessed for intra- and inter-operator variation, and the effects of cryopreservation. Cryopreserved samples were shipped to a second laboratory in order to assess inter-laboratory variation. BMEM frequencies were very strongly correlated when comparing fresh and frozen samples processed by the same operator, and were also very strongly correlated when comparing 2 operators in the same laboratory. Results were slightly less consistent when samples were processed in different laboratories although correlation between the 2 measurements was still very strong. Although cell viability was reduced in some cryopreserved samples due to higher temperatures during transportation, BMEM could still be quantified. These results demonstrate the reproducibility of the ELISpot assay across operators and laboratories, and support the use of cryopreserved samples in future BMEM studies.
    Human vaccines 06/2014; 10(8). · 3.14 Impact Factor
  • Andrew J Pollard
    Indian pediatrics. 06/2014; 51(6):445-6.
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    ABSTRACT: Detailed characterization of the protective T cell response in salmonellosis is a pressing unmet need in light of the global burden of human Salmonella infections and the likely contribution of CD4 T cells to immunity against this intracellular infection. In previous studies screening patient sera against antigen arrays, SseB was noteworthy as a serodominant target of adaptive immunity, inducing significantly raised antibody responses in HIV seronegative compared to seropositive subjects. SseB is a secreted protein, part of the Espa superfamily, localized to the bacterial surface and forming part of the translocon of the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We demonstrate here that SseB is also a target of CD4 T cell immunity, generating a very substantial response after experimental infection in human volunteers, with around 0.1% of the peripheral repertoire responding to it. HLA-DR/peptide binding studies indicate that this protein encompasses a number of peptides with ability to bind to several different HLA-DR alleles. Of these, peptide 11 (p11) was shown in priming of both HLA-DR1 and HLA-DR4 transgenic mice to contain an immunodominant CD4 epitope. Analysis of responses in human donors showed immunity focused on p11 and another epitope in peptide 2. The high frequency of SseB-reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled with previous observations of serodominance and protective vaccination in mouse challenge experiments, make SseB a plausible candidate for next generation Salmonella vaccines. This article is protected by copyright. All rights reserved.
    Immunology 05/2014; · 3.71 Impact Factor
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    ABSTRACT: Nearly all licensed vaccines have been developed to confer protection against infectious diseases by stimu- lating the production of antibodies by B cells, but the nature of a successful antibody response has been diffi- cult to capture. Recent advances in next-generation sequencing (NGS) technology have allowed high-reso- lution characterization of the antibody repertoire, and of the changes that occur following vaccination. These approaches have yielded important insights into the B cell response, and have raised the possibility of using specific antibody sequences as measures of vaccine immunogenicity. Here, we review recent findings based on antibody repertoire sequencing, and discuss poten- tial applications of these new technologies and of the analyses of the increasing volume of antibody sequence data in the context of vaccine development.
    Trends in Immunology 05/2014; · 9.49 Impact Factor
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    ABSTRACT: The introduction of the serogroup C meningococcal (MenC) conjugate vaccination has successfully controlled the burden of disease associated with this serogroup in many countries. However, considerable inter-individual variation is observed in immune responses to MenC vaccine, and little is understood of the determinants of this variability. Previously, we reported an association between single nucleotide polymorphisms (SNPs) in TLR3 and CD44 and the persistence of MenC vaccine immunity. Here we further examine polymorphisms within these two candidate genes and immune responses to MenC vaccination. Specific-IgG concentrations and serum bactericidal assay (SBA) titres were measured one month after a primary course of MenC vaccination in 318 human infants. Tagging SNPs (TagSNPs) within TLR3 and CD44 were genotyped and regional imputations carried out to screen these genes for variations associated with immunological responses to MenC vaccination. This study reports an association between an exonic variant (rs3775290, P=0.025) in TLR3 and MenC IgG concentrations, as well as an association between three SNPs in CD44 (rs3794109, P=0.021; rs3794110, P=0.022; rs112762, P=0.049) and MenC SBA titres. These data support our previous findings of an association between SNPs in TLR3 and CD44, and present novel findings implicating exonic variants in these genes with MenC vaccine responses.
    Vaccine 04/2014; · 3.77 Impact Factor
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    ABSTRACT: A serogroup B meningococcal vaccine (4CMenB) has been licensed by the European commission for use in various infant schedules. However, data are limited on persistence of serum bactericidal antibodies (SBA), which is necessary to inform cost-effectiveness analysis. Sera were obtained from three groups of 5 year-old children previously immunized at 6, 8, 12 and 40 months with either 4CMenB or rMenB (which lacks the outer membrane vesicle of 4CMenB) or at 40 and 42 months with 4CMenB only. Forty-nine control children were also recruited and blood obtained before and after 2 doses of 4CMenB at 60 and 62 months of age. Sera were tested for SBA to meningococcal B (MenB) reference strains. At 5 years of age, 67% of those receiving 4CMenB in infancy had SBA titers ≥1:4 for strain 44/76, 100% for 5/99, 17% for NZ98/254 and 45% for M10713. Results for rMenB recipients varied from 0 (NZ98/254) to 100% (5/99). Of those immunized with 4CMenB at 40 and 42 months, 38% had SBA titers ≥1:4 at age five for 44/76, 100% for 5/99, 0% (NZ98/254) and 83% (M10713). Amongst controls, SBA titers were ≥1:4 in 4% (H44/76, 5/99), 0% (NZ98/254) and 67% (M10713) at baseline, increasing to 100% (H44/76 and 5/99), 89% (NZ98/254) and 97% (M10713) post-immunization. The variable rates of waning of antibody to the four components of 4CMenB complicates estimates of duration of protection and should be taken into account in cost-effectiveness analyses. A two-dose schedule of 4CMenB in 5 year-old children was immunogenic.
    The Pediatric Infectious Disease Journal 04/2014; · 3.57 Impact Factor
  • Sophie M Andrews, Andrew J Pollard
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    ABSTRACT: Neisseria meningitidis is an important cause of invasive bacterial infection in children worldwide. Although serogroup C meningococcal disease has all but disappeared in the past decade as a direct result of immunisation programmes in Europe, Canada, and Australia, meningitis and septicaemia caused by serogroup B meningococci remain uncontrolled. A vaccine (4CMenB) has now been licensed for use in the European Union, comprising three immunogenic antigens (identified with use of reverse vaccinology) combined with bacterial outer-membrane vesicles. The vaccine has the potential to reduce mortality and morbidity associated with serogroup B meningococci infections, but uncertainty remains about the breadth of protection the vaccine might induce against the diverse serogroup B meningococci strains that cause disease. We discuss drawbacks in the techniques used to estimate coverage and potential efficacy of the vaccine, and their effects on estimates of cost-effectiveness, both with and without herd immunity. For parents, and clinicians treating individual patients, the predicted benefits of vaccination outweigh existing uncertainties if any cases can be prevented, but future use of the vaccine must be followed by rigorous post-implementation surveillance to reassess its value to health systems with directly recorded epidemiological data.
    The Lancet Infectious Diseases 03/2014; · 19.97 Impact Factor
  • Andrew J Pollard, Andrew Riordan, Mary Ramsay
    The Lancet 03/2014; · 39.21 Impact Factor
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    ABSTRACT: The introduction of vaccines containing the capsular polysaccharides of N. meningitidis, S. pneumonia, and H. influenzae type b has driven a significant reduction in cases of disease caused by these bacteria. The polysaccharide-specific antibody responses following vaccination are well characterized, however less is known about the B cells underlying this response. Here, we summarize the plasma cell (PC) and memory B cell (BMEM) responses following plain polysaccharide and protein-polysaccharide conjugate vaccination, drawing together studies covering a range of vaccines and age groups. These studies show that infant primary PC and BMEM responses to polysaccharide-conjugate vaccines are low in relation to older age groups but are significantly higher following booster doses. PC kinetics have generally been found to follow a similar pattern irrespective of vaccine type or age group, whereas divergent BMEM responses have been reported following plain polysaccharide and conjugate vaccination. A degree of correlation between early BMEM responses and maintenance of protective antibody levels has been identified in some studies, but the relationship between the two remains unclear. Identification of the B cell subsets involved and the mechanisms by which they are induced may provide a better understanding of the role of B cells in maintaining protective immunity through vaccination.
    Human vaccines 03/2014; 10(6). · 3.14 Impact Factor
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    ABSTRACT: Infection with Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae causes substantial mortality and long-term morbidity in children. We know of no study to assess the long-term trends in hospital admission rates for meningitis and septicaemia caused by these pathogens in children in England. We aimed to do such a study using routinely reported data in England. In this population-based observational study, we used datasets that include routinely collected administrative statistics for hospital care: the Hospital In-Patient Enquiry (data for England from 1968 to 1985), the Hospital Episode Statistics dataset (data for England from 1989 onwards), and the Oxford record linkage study (data for Oxfordshire and surrounding areas from 1963 to 2011). We analysed annual age-specific and age-standardised admission rates in children younger than 15 years with H influenzae, meningococcal and pneumococcal meningitis, and septicaemia. We saw a reduction in hospital admission rates for childhood invasive bacterial disease after the introduction of conjugate vaccines against H influenzae, N meningitidis, and S pneumoniae in England. Annual incidence of H influenzae meningitis per 100 000 children decreased from 6·72 admissions (95% CI 6·18-7·26) in 1992 to 0·39 admissions (0·26-0·52) in 1994, after the introduction of routine H influenzae type b vaccination. We saw a small rise in admissions in the early 2000s, peaking at 1·24 admissions per 100 000 children (0·99-1·48) in 2003, which decreased to 0·28 per 100 000 children (0·17-0·39) by 2008 after the introduction of catch-up (2003) and routine (2006) booster programmes for young children. Meningococcal disease increased during the 1990s, reaching a peak in 1999, with 34·54 admissions (33·30-35·78) per 100 000 children. Hospital admissions decreased after the meningococcal serogroup C vaccine was introduced in 1999 and was 12·40 admissions (11·68-13·12) per 100 000 in 2011. Admissions for invasive pneumococcal disease increased from the 1990s reaching a peak in 2006 at 4·45 admissions for meningitis (95% CI 4·0-4·9) per 100 000 children and 2·81 admissions for septicaemia (2·45-3·17) per 100 000 children. A reduction in admissions occurred after the introduction of the pneumococcal conjugate vaccine in 2006: hospital admission rates in 2011 were 2·03 per 100 000 children for meningitis and 1·12 per 100 000 children for septicaemia. Vaccine-preventable invasive bacterial disease in children has decreased substantially in England in the past five decades, most notably with the advent of effective conjugate vaccines since the 1990s. Ongoing disease surveillance and continued development and implementation of vaccines against additional pneumococcal serotypes and serogroup B meningococcal disease are important. None.
    The Lancet Infectious Diseases 03/2014; · 19.97 Impact Factor
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    ABSTRACT: Background. Typhoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. Until 1974, a human challenge model advanced understanding of typhoid and was used in vaccine development. We set out to establish a new human challenge model and ascertain the S. Typhi (Quailes strain) inoculum required for an attack rate of 60-75% in typhoid-naïve volunteers when ingested with sodium bicarbonate solution. Methods. Groups of healthy consenting adults ingested escalating dose levels of S. Typhi and were closely monitored in an outpatient setting for 2 weeks. Antibiotic treatment was initiated if a 'typhoid diagnosis' occurred (temperature ≥38°C sustained ≥12 hours or bacteraemia) or at day 14 in those remaining untreated. Results. Two dose levels (10(3) or 10(4) CFU) were required to achieve the primary objective, resulting in attack rates of 55% (11/20) or 65% (13/20), respectively. Challenge was well tolerated; 4/40 participants fulfilled pre-specified criteria for severe infection. Most diagnoses (87.5%) were blood culture confirmed while asymptomatic bacteraemia and stool shedding of S. Typhi was also observed. Participants who developed typhoid infection demonstrated serological responses to flagellin and LPS antigens by day 14; no anti-Vi antibody responses were detected however. Conclusions. Human challenge with a small inoculum of virulent S. Typhi administered in bicarbonate solution can be performed safely using an ambulant model design to advance understanding of host-pathogen interactions and immunity. This model should expedite development of diagnostics, vaccines and therapeutics for typhoid control.
    Clinical Infectious Diseases 02/2014; · 9.37 Impact Factor
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    ABSTRACT: Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease.
    PLoS ONE 01/2014; 9(1):e85055. · 3.53 Impact Factor
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    ABSTRACT: Background. Protection against, Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (+/-booster) Hib vaccination. Methods. Anti-PRP IgG concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month and 1 year after the booster in 250 healthy 6 to 12 year old children in an open label phase IV clinical study. Results. Six to twelve years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG GMC were 3.11 µg/ml and 0.71 µg/ml and proportions with anti-PRP IgG≥1.0 µg/ml were 79% and 43% respectively in children who had, or had not, received a 4(th) Hib dose (mean age 3.9 years). Higher baseline and post Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a 4(th) Hib. Conclusions. Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies in order to sustain individual and population immunity against encapsulated bacteria in early childhood.
    Clinical Infectious Diseases 01/2014; · 9.37 Impact Factor
  • Andrew J Pollard, Andrew Riordan, Mary Ramsay
    BMJ (online) 01/2014; 348:g2859. · 17.22 Impact Factor
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    ABSTRACT: Pneumococcal disease is a significant cause of morbidity and mortality in young children in Nepal, and currently available pneumococcal conjugate vaccines offer moderate coverage of invasive disease isolates.
    PLoS ONE 01/2014; 9(6):e98739. · 3.53 Impact Factor
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    ABSTRACT: The success of immunisation programmes depends on the quality with which they are administered. The Vaccine Advice for CliniCians Service (VACCSline) is an advice service to support immunisers and promote excellence in immunisation practice, through specialist guidance and local education, covering a catchment population of two million people. All enquiries are recorded onto a database and categorised. Vaccine error is selected when a vaccine has not been prepared or administered according to national recommendations or relevant expert guidance.
    Quality in primary care 01/2014; 22(3):139-46.

Publication Stats

3k Citations
1,515.87 Total Impact Points

Institutions

  • 2012–2014
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
    • University of Southampton
      Southampton, England, United Kingdom
    • Patan Academy of Health Sciences
      Lalitpur, Central Region, Nepal
  • 2002–2014
    • University of Oxford
      • Department of Paediatrics
      Oxford, England, United Kingdom
    • Sheffield Children's NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 2013
    • University of Melbourne
      • Department of Paediatrics
      Melbourne, Victoria, Australia
  • 2010–2013
    • Public Health England
      • Modelling and Economics Unit
      Londinium, England, United Kingdom
  • 2011
    • Mahidol University
      • Faculty of Tropical Medicine
      Krung Thep, Bangkok, Thailand
    • The University of Manchester
      • Faculty of Life Sciences
      Manchester, England, United Kingdom
  • 2002–2011
    • Oxford University Hospitals NHS Trust
      • Department of Paediatrics
      Oxford, England, United Kingdom
  • 2009
    • Luton and Dunstable Hospital NHS Foundation Trust
      Luton, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2007
    • Sanofi Pasteur MSD
      Lyons, Rhône-Alpes, France
    • Children's Hospital Oakland Research Institute
      Oakland, California, United States
  • 2006–2007
    • St George's, University of London
      Londinium, England, United Kingdom
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
    • University of Bristol
      • School of Cellular and Molecular Medicine
      Bristol, ENG, United Kingdom
  • 2005
    • KEMRI-Wellcome Trust Research Programme
      Kilifi, Kilifi, Kenya
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia
  • 2004–2005
    • St. George's School
      Middletown, Rhode Island, United States
  • 2001–2004
    • Children's & Women's Health Centre of British Columbia
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
  • 2000–2004
    • University of British Columbia - Vancouver
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
  • 2003
    • University of Leicester
      Leiscester, England, United Kingdom
  • 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
  • 1997
    • Queen Mary, University of London
      • Centre for Paediatrics
      London, ENG, United Kingdom
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
    • Canterbury District Health Board
      Christchurch, Canterbury Region, New Zealand