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• Journal article
  Lefevre EA, Carr BV, Inman CF, Prentice H, Brown IH, Brookes SM, Garcon F, Hill ML, Iqbal M, Elderfield RA, Barclay WS, Gubbins S, Bailey M, Charleston Bet al., 2012,

  Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

  , PLOS One, Vol: 7, ISSN: 1932-6203

  Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.

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• Journal article
  Fouchier RAM, Garcia-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Metten-Leiter TC, Osterhaus ADME, Palese P, Peiris JSM, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RGet al., 2012,

  Pause on Avian Flu Transmission Research

  , SCIENCE, Vol: 335, Pages: 400-401, ISSN: 0036-8075
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  • Citations: 48
• Conference paper
  Sridhar S, Begom S, Bermingham A, Ziegler T, Roberts KL, Barclay WS, Openshaw P, Lalvani Aet al., 2012,

  Predominance of heterosubtypic IFN-gamma-only-secreting effector memory T cells in pandemic H1N1 naive adults

  , Pages: 2913-2924, ISSN: 1521-4141

  The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-gamma and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naive individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-gamma-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-gamma-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-gamma-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.

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• Journal article
  van Doremalen N, Shelton H, Roberts KL, Jones IM, Pickles RJ, Thompson CI, Barclay WSet al., 2011,

  A Single Amino Acid in the HA of pH1N1 2009 Influenza Virus Affects Cell Tropism in Human Airway Epithelium, but Not Transmission in Ferrets

  , PLOS ONE, Vol: 6, ISSN: 1932-6203
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  • Citations: 24
• Journal article
  Roberts KL, Shelton H, Scull M, Pickles R, Barclay WSet al., 2011,

  Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity <i>in vivo</i>

  , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 1822-1831, ISSN: 0022-1317
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  • Citations: 40
• Journal article
  Foeglein A, Loucaides EM, Mura M, Wise HM, Barclay WS, Digard Pet al., 2011,

  Influence of PB2 host-range determinants on the intranuclear mobility of the influenza A virus polymerase

  , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 1650-1661, ISSN: 0022-1317
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  • Citations: 46
• Journal article
  Brookes DW, Miah S, Lackenby A, Hartgroves L, Barclay WSet al., 2011,

  Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitness

  , JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 66, Pages: 466-470, ISSN: 0305-7453
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  • Citations: 51
• Journal article
  Loureiro S, Ren J, Phapugrangkul P, Colaco CA, Bailey CR, Shelton H, Molesti E, Temperton NJ, Barclay WS, Jones IMet al., 2011,

  Adjuvant-Free Immunization with Hemagglutinin-Fc Fusion Proteins as an Approach to Influenza Vaccines

  , JOURNAL OF VIROLOGY, Vol: 85, Pages: 3010-3014, ISSN: 0022-538X
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  • Citations: 36
• Journal article
  Shelton H, Ayora-Talavera G, Ren J, Loureiro S, Pickles RJ, Barclay WS, Jones IMet al., 2011,

  Receptor Binding Profiles of Avian Influenza Virus Hemagglutinin Subtypes on Human Cells as a Predictor of Pandemic Potential

  , JOURNAL OF VIROLOGY, Vol: 85, Pages: 1875-1880, ISSN: 0022-538X
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  • Citations: 40
• Journal article
  Jackson D, Elderfield RA, Barclay WS, 2011,

  Molecular studies of influenza B virus in the reverse genetics era

  , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 1-17, ISSN: 0022-1317
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  • Citations: 51

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