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  • Journal article
    Harker JA, Yamaguchi Y, Culley FJ, Tregoning JS, Openshaw PJMet al., 2014,

    Delayed sequelae of neonatal RSV infection are dependent on cells of the innate immune system

    , Journal of Virology, ISSN: 0022-538X

    Infection with respiratory syncytial virus (RSV) in neonatal mice leads to exacerbated disease if mice are re-infected with the same virus as adults. Both T cells and host MHC genotype contribute to this phenomenon, but the part played by innate immunity has not been defined. Since macrophages and natural killer (NK) cells play key roles in regulating inflammation during RSV infection of adult mice, we studied the role of these cells in exacerbated inflammation following neonatal RSV sensitization/adult re-infection. Compared to those undergoing primary adult infection, neonatally sensitized mice showed enhanced airway fluid levels of interleukin-6 (IL-6), interferon alpha (IFNα), CXCL1 (KC) and tumor necrosis factor alpha (TNFα) at 12-24h, and IL-4, IL-5, IFNγ and CCL11 (eotaxin) at day 4 after re-infection. Weight loss during re-infection was accompanied by an initial influx of NK cells and granulocytes into the airways and lungs, followed by T cells. NK depletion during re-infection attenuated weight loss, but did not alter T cell responses. Depleting alveolar macrophages with inhaled clodronate liposomes reduced both NK and T cell numbers and attenuated weight loss. These findings indicate a hitherto unappreciated role for the innate immune response in governing the pathogenic recall responses to RSV infection.

  • Journal article
    Moog C, Dereuddre-Bosquet N, Teillaud J-L, Biedma ME, Holl V, Van Ham G, Heyndrickx L, Van Dorsselaer A, Katinger D, Vcelar B, Zolla-Pazner S, Mangeot I, Kelly C, Shattock RJ, Le Grand Ret al., 2014,

    Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques

    , MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 46-56, ISSN: 1933-0219
  • Conference paper
    Tregoning JS, Wang B, McDonald JU, Yamaguchi Y, Harker JA, Goritzka M, Johansson C, Bukreyev A, Collins PL, Openshaw PJet al., 2013,

    Respiratory syncytial virus (RSV) infection during early life suppresses antibody responses by the induction of interferon gamma

    , Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 104-104, ISSN: 0019-2805
  • Journal article
    Everitt AR, Clare S, McDonald JU, Kane L, Harcourt K, Ahras M, Lall A, Hale C, Rodgers A, Young DB, Haque A, Billker O, Tregoning JS, Dougan G, Kellam Pet al., 2013,

    Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model

    , PLOS ONE, Vol: 8, ISSN: 1932-6203
  • Journal article
    Tregoning JS, Buffa V, Oszmiana A, Klein K, Walters AA, Shattock RJet al., 2013,

    A "Prime-Pull" Vaccine Strategy Has a Modest Effect on Local and Systemic Antibody Responses to HIV gp140 in Mice

    , PLOS One, Vol: 8, ISSN: 1932-6203

    One potential strategy for the prevention of HIV infection is to induce virus specific mucosal antibody that can act as animmune barrier to prevent transmission. The mucosal application of chemokines after immunisation, termed ‘‘prime-pull’’,has been shown to recruit T cells to mucosal sites. We wished to determine whether this strategy could be used to increaseB cells and antibody in the vaginal mucosa following immunisation with an HIV antigen. BALB/c mice were immunisedintranasally with trimeric gp140 prior to vaginal application of the chemokine CCL28 or the synthetic TLR4 ligand MPLA,without antigen six days later. There was no increase in vaginal IgA, IgG or B cells following the application of CCL28,however vaginal application of MPLA led to a significant boost in antigen specific vaginal IgA. Follow up studies toinvestigate the effect of the timing of the ‘‘pull’’ stimulation demonstrated that when given 14 days after the initialimmunisation MPLA significantly increased systemic antibody responses. We speculate that this may be due to residualinflammation prior to re-immunisation. Overall we conclude that in contrast to the previously observed effect on T cells, theuse of ‘‘prime-pull’’ has only a modest effect on B cells and antibody.

  • Conference paper
    Cosgrove CA, Lacey C, Cope AV, Bartolf A, Morris G, Yan C, Baden S, Cole T, Carter D, Brodnicki E, Stoehr W, McCormack S, Shattock RJet al., 2013,

    A Phase I Clinical Trial of an HIV-1(CN54), Clade C, Trimeric Envelope Vaccine Delivered by Parenteral, Nasal and Vaginal Routes of Immunisation

    , Conference on AIDS Vaccine, Publisher: MARY ANN LIEBERT, INC, Pages: A9-A9, ISSN: 0889-2229
  • Conference paper
    Herrera C, Schuetz A, Olejniczak N, Assawadarachai V, Karasavva N, Nitayaphan S, Kaewkungwal J, Ngauy V, Pitisuttithum P, Rerks-Ngarm S, Michael NL, O'Connell RJ, Excler J, Shattock RJ, Kim JHet al., 2013,

    Preliminary Evaluation of Mucosal Immune Responses with Mucosal Explants in Humans Vaccinated with ALVAC/AIDSVAX B/E During the Ongoing RV305 Trial

    , Conference on AIDS Vaccine, Publisher: MARY ANN LIEBERT, INC, Pages: A181-A181, ISSN: 0889-2229
  • Conference paper
    Herrera C, Olejniczak N, Karasavva N, Rasmussen TA, Rasmussen K, Veazey RS, Kim JH, Shattock RJet al., 2013,

    Use of Tissue Explants to Evaluate Mucosal Immune Responses in Non-Human Primates (NHPs) Vaccinated with ALVAC/AIDSVAX B/E

    , Conference on AIDS Vaccine, Publisher: MARY ANN LIEBERT, INC, Pages: A105-A105, ISSN: 0889-2229
  • Journal article
    Klein K, Veazey RS, Warrier R, Hraber P, Doyle-Meyers LA, Buffa V, Liao H-X, Haynes BF, Shaw GM, Shattock RJet al., 2013,

    Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

    , JOURNAL OF VIROLOGY, Vol: 87, Pages: 11604-11616, ISSN: 0022-538X
  • Journal article
    Mann JFS, McKay PF, Arokiasamy S, Patel RK, Klein K, Shattock RJet al., 2013,

    Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection

    , JOURNAL OF CONTROLLED RELEASE, Vol: 170, Pages: 452-459, ISSN: 0168-3659

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