William Elsley

Publications (21) View all

• Article: Novel vaccine and gene therapy approaches against HIV-AIDS

  A Das, W Kleibeuker, B Klaver, K von Eije, YP Liu, O ter Brake, M Centlivre, N Legrand, N Berry, H Tudor, M Page, M Robinson, R Quartey-Papafio, W Elsley, B Li, M Manoussaka, R Stebbings, M Cranage, N Almond, B Berkhout
  01/2009;
• Source

  Available from: Richard Stebbings

  Article: Preparation and characterization of new challenge stocks of SIVmac32H J5 following rapid serial passage of virus in vivo.

  D Ferguson, A Wade-Evans, W Elsley, R Sangster, P Silvera, S MacManus, G Davis, T Corcoran, N Berry, S Brown, A Jenkins, J Cowie, M Sethi, R Hull, R Stebbings, J Lines, S Norley, E J Stott, N Almond
  [show abstract] [hide abstract]
  ABSTRACT: A new challenge stock of the simian immunodeficiency virus SIVmacJ5 has been produced following passage in vivo. SIVmacJ5 3/92 (J5M), was passaged serially through cynomolgus macaques (Macaca fascicularis) by intravenous inoculation of infected spleen cells isolated and prepared 14 days post-infection. Two challenge stocks, SIVmacJ5 S61MLN and SIVmacJ5 S62spl, were prepared by culture of lymphoid tissue ex vivo. These virus stocks appeared better adapted for replication in M. fascicularis as demonstrated by a greater persistence of recoverable live virus from the periphery and increased pathology in lymphoid tissues 20 weeks post-challenge as detected by immunohistochemistry. Sequence analysis of the envelope gene from these stocks did not identify marked diversification of sequence as a result of this procedure. These stocks display more robust peripheral persistence and tissue pathology in cynomolgus macaques and should prove valuable analysing recombinant vaccines based upon SIVmacJ5 transgenes.
  Journal of Medical Primatology 07/2007; 36(3):131-42. · 1.30 Impact Factor
• Article: Immunological responses and viral modulatory effects of vaccination with recombinant modified vaccinia virus Ankara (rMVA) expressing structural and regulatory transgenes of simian immunodeficiency virus (SIVmac32H/J5M).

  N Berry, R Stebbings, S Brown, P Christian, R Thorstensson, R K Ahmed, L Davis, D Ferguson, N D'Arcy, W Elsley, R Hull, J Lines, A Wade-Evans, J Stott, N Almond
  [show abstract] [hide abstract]
  ABSTRACT: The immunogenicity and protective efficacy of recombinant modified vaccinia virus Ankara (rMVA) vectors expressing structural (gag/pol, env) and regulatory (tat, rev, nef) genes of SIVmac251/32H-J5 (rMVA-J5) were assessed. Immunization with rMVA constructs (2.5 x 10(7) IU) 32, 20 and 8 weeks pre-challenge was compared with 32 and 20 weeks but with a final boost 8 weeks pre-challenge with 2 x 10(6) fixed-inactivated HSC-F4 cells infected with SIVmac32H. Controls received rMVA vectors expressing an irrelevant transgene or were naïve challenge controls. All received 10 MID(50) SIVmac32H/J5 intravenously. Vaccinates immunized with rMVA-J5 exhibited significant, albeit transient, control of peak primary viraemia despite inconsistent and variable immune responses elicted by vaccination. Humoral and cellular responses to Env were most consistent, with lower responses to Nef, Rev and Tat. Increasing titres of anti-vaccinia neutralizing antibodies reflected the number and dose of rMVA inoculations. Improved combinations of viral vectors are required to elicit appropriate immune responses to control viral replication.
  Journal of Medical Primatology 05/2007; 36(2):80-94. · 1.30 Impact Factor
• Source

  Available from: William Elsley

  Article: Mechanisms of loss of functional dendritic cells in HIV-1 infection.

  S C Knight, W Elsley, H Wang
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  ABSTRACT: Dendritic cells (DC) are lost from blood and skin during injection with HIV-1; those remaining show a reduced capacity to stimulate T cell proliferation [S. C. Knight, AIDS 10, 807-817]. Our recent studies investigate mechanisms underlying these effects. DC exposed to HIV-1 vitro can act as targets for cytotoxic T cells, although optimal killing was not obtained until DC were exposed to HIV-1 for 3 days. This cytotoxicity may provide a feedback mechanism by which DC that have presented antigens are removed. However, this effect could also contribute to the reduction in DC during persistent infection. We have also investigated the effect of exposure to HIV-1 on DC function. DC exposed to HIV-1 IIIB virus for 2 h stimulated primary proliferative and cytotoxic T cell responses in vitro; these effects may be similar to those occurring during the early activation of protective antiviral immunity in vivo. After exposure of DC to virus for 5 days, stimulation of allogeneic T cells was reduced. However, a different situation applied when using DC developed from CD34+ cord blood stem cells under the influence of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha that were exposed at 24 h to the same virus. These DC showed low levels of infection similar to peripheral blood DC but in contrast stimulated normal allogeneic T cell proliferation. The capacity of DC exposed to HIV-1 to stimulate T cell proliferation or to show a blocked stimulatory capacity may thus depend not only on the length of the exposure to virus but also on the maturational state of the DC. Loss in DC numbers and function on exposure to HIV-1 may result in lower levels of stimulation of T cells, which in turn may be instrumental in reduction of T cell numbers.
  Journal of Leukocyte Biology 08/1997; 62(1):78-81. · 4.99 Impact Factor
• Article: Dendritic cells, apoptosis and murine retrovirus.

  G M Woods, D I Gabrilovich, W Elsley, N English, S C Knight
  Advances in experimental medicine and biology 02/1995; 378:493-6. · 1.09 Impact Factor